--
--

\restrict HggCO2gs9B0mxkkOraMToUnv6d2ER0HEvqGhvM5sjPevLwYpbD4EwK9neBB3asb


SELECT pg_catalog.set_config('search_path', '', false);

--
-- Name: cpic; Type: SCHEMA; Schema: -; Owner: -
--

CREATE SCHEMA cpic;


--
-- Name: increment_version(); Type: FUNCTION; Schema: cpic; Owner: -
--

CREATE FUNCTION cpic.increment_version() RETURNS trigger
    LANGUAGE plpgsql
    AS $$
BEGIN
  new.version := new.version + 1;
  return new;
END;
$$;


--
-- Name: pharmgkb_guideline_alleles(text); Type: FUNCTION; Schema: cpic; Owner: -
--

CREATE FUNCTION cpic.pharmgkb_guideline_alleles(pharmgkbdrugid text) RETURNS TABLE(genesymbol text, chr text, lookupmethod text, alleles text[])
    LANGUAGE sql STABLE
    AS $$
select
    a.genesymbol,
    g.chr,
    g.lookupmethod,
    array_agg(distinct a.name order by a.name) as alleles
from allele a join gene g on a.genesymbol=g.symbol
where
    a.clinicalfunctionalstatus is not null
    and g.lookupmethod!='ALLELE_STATUS'
    and a.genesymbol in (
        select distinct jsonb_object_keys(p.lookupkey) as genes
        from recommendation p join guideline g on p.guidelineid = g.id join drug d on p.drugid=d.drugid
        where d.pharmgkbid=pharmgkbdrugid
    )
group by a.genesymbol, g.chr, g.lookupmethod
union all
select
    g.symbol as genesymbol,
    g.chr,
    g.lookupmethod,
    array_agg(distinct a.value order by a.value) as alleles
from
    recommendation r
    join drug d on r.drugid = d.drugid,
    jsonb_each_text(r.lookupkey) a
    join gene g on (a.key=g.symbol)
where
    r.allelestatus is not null
    and g.lookupmethod='ALLELE_STATUS'
    and d.pharmgkbid=pharmgkbdrugid
    and upper(a.value) != 'NO RESULT'
group by g.symbol, g.chr, g.lookupmethod
$$;


--
-- Name: FUNCTION pharmgkb_guideline_alleles(pharmgkbdrugid text); Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON FUNCTION cpic.pharmgkb_guideline_alleles(pharmgkbdrugid text) IS 'For a given PharmGKB drug ID, list the alleles that are options for looking up recommendations';


--
-- Name: pharmgkb_guideline_recommendation(text, text); Type: FUNCTION; Schema: cpic; Owner: -
--

CREATE FUNCTION cpic.pharmgkb_guideline_recommendation(drugidarg text, lookupkeyarg text) RETURNS TABLE(drugname text, recommendationid integer, implications jsonb, drugrecommendation text, classification text, phenotypes jsonb, activityscore jsonb, allelestatus jsonb, population text, comments text)
    LANGUAGE sql STABLE
    AS $$
select
    d.name as drugname,
    r.id as recommendationid,
    r.implications,
    r.drugrecommendation,
    r.classification,
    r.phenotypes,
    r.activityscore,
    r.allelestatus,
    r.population,
    r.comments
from recommendation r join drug d on r.drugid = d.drugid join guideline g on r.guidelineid = g.id
where lookupkey <@ (
    select jsonb_object_agg(a.key, coalesce(d.lookupkey -> a.key, a.value)) as lookup
    from
        json_each(lookupkeyArg::json) a
            left join diplotype d on (d.diplotypekey=jsonb_build_object(a.key, a.value))
)
  and d.pharmgkbid=drugidArg
$$;


--
-- Name: FUNCTION pharmgkb_guideline_recommendation(drugidarg text, lookupkeyarg text); Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON FUNCTION cpic.pharmgkb_guideline_recommendation(drugidarg text, lookupkeyarg text) IS 'For a given PharmGKB guideline and genotype lookup JSON key, give the matching recommendations';


--
-- Name: pharmgkb_recommendation(text); Type: FUNCTION; Schema: cpic; Owner: -
--

CREATE FUNCTION cpic.pharmgkb_recommendation(lookupkeyarg text) RETURNS TABLE(drugname text, drugid text, recommendationid integer, implications jsonb, drugrecommendation text, classification text, phenotypes jsonb, activityscore jsonb, allelestatus jsonb, population text, comments text, guidelineurl text)
    LANGUAGE sql STABLE
    AS $$
select
    d.name as drugname,
    d.pharmgkbid as drugid,
    r.id as recommendationid,
    r.implications,
    r.drugrecommendation,
    r.classification,
    r.phenotypes,
    r.activityscore,
    r.allelestatus,
    r.population,
    r.comments,
    g.url as guidelineurl
from recommendation r join drug d on r.drugid = d.drugid join guideline g on r.guidelineid = g.id
where lookupkey <@ (
    select jsonb_object_agg(a.key, coalesce(d.lookupkey -> a.key, a.value)) as lookup
    from
        json_each(lookupKeyArg::json) a
            left join diplotype d on (d.diplotypekey=jsonb_build_object(a.key, a.value))
)
$$;


--
-- Name: FUNCTION pharmgkb_recommendation(lookupkeyarg text); Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON FUNCTION cpic.pharmgkb_recommendation(lookupkeyarg text) IS 'For a given genotype lookup JSON key, give the matching recommendations for all available drugs';


--
-- Name: cpic_id; Type: SEQUENCE; Schema: cpic; Owner: -
--

CREATE SEQUENCE cpic.cpic_id
    START WITH 110000
    INCREMENT BY 1
    NO MINVALUE
    NO MAXVALUE
    CACHE 1;




--
-- Name: drug; Type: TABLE; Schema: cpic; Owner: -
--

CREATE TABLE cpic.drug (
    drugid character varying(20) NOT NULL,
    name text NOT NULL,
    pharmgkbid character varying(20),
    rxnormid character varying(20),
    drugbankid character varying(20),
    atcid text[],
    umlscui character varying(20),
    flowchart text,
    version integer DEFAULT 1,
    guidelineid integer
);


--
-- Name: TABLE drug; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON TABLE cpic.drug IS 'A clinically-used drug.';


--
-- Name: COLUMN drug.drugid; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.drug.drugid IS 'A unique identifier for this drug in the form "source:id" where source is some outside knowledge resource and id is their identifier, primary key';


--
-- Name: COLUMN drug.name; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.drug.name IS 'The generic name for this drug, lower-cased, required';


--
-- Name: COLUMN drug.pharmgkbid; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.drug.pharmgkbid IS 'The PharmGKB ID for this drug, optional';


--
-- Name: COLUMN drug.rxnormid; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.drug.rxnormid IS 'The RxNorm ID for this drug, optional';


--
-- Name: COLUMN drug.drugbankid; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.drug.drugbankid IS 'The DrugBank ID for this drug, optional';


--
-- Name: COLUMN drug.atcid; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.drug.atcid IS 'One or more ATC IDs for this drug in an array, optional';


--
-- Name: COLUMN drug.umlscui; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.drug.umlscui IS 'The UMLS Concept Unique ID for this drug, optional';


--
-- Name: COLUMN drug.flowchart; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.drug.flowchart IS 'URL for the flow chart image of this drug';


--
-- Name: COLUMN drug.guidelineid; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.drug.guidelineid IS 'The guideline this drug is part of a guideline, null means not a part of any guideline';


--
-- Name: guideline; Type: TABLE; Schema: cpic; Owner: -
--

CREATE TABLE cpic.guideline (
    id integer DEFAULT nextval('cpic.cpic_id'::regclass) NOT NULL,
    version integer DEFAULT 1,
    name text NOT NULL,
    url text,
    pharmgkbid text[],
    genes text[],
    notesonusage text,
    clinpgxid text
);


--
-- Name: TABLE guideline; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON TABLE cpic.guideline IS 'A guideline for a drug or group of drugs';


--
-- Name: COLUMN guideline.id; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.guideline.id IS 'A synthetic numerical ID, primary key';


--
-- Name: COLUMN guideline.version; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.guideline.version IS 'The version number, iterates on modification';


--
-- Name: COLUMN guideline.name; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.guideline.name IS 'The name (title) of this guideline, required';


--
-- Name: COLUMN guideline.url; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.guideline.url IS 'The URL of this guideline on the cpicpgx.org domain, optional';


--
-- Name: COLUMN guideline.pharmgkbid; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.guideline.pharmgkbid IS 'The IDs from PharmGKB for their annotations of this guideline, optional';


--
-- Name: COLUMN guideline.genes; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.guideline.genes IS 'The subject genes of this guideline';


--
-- Name: COLUMN guideline.notesonusage; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.guideline.notesonusage IS 'Notes about using a particular guideline within this system. This may include. You may find information here when data for a guideline seems missing or incomplete.';


--
-- Name: COLUMN guideline.clinpgxid; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.guideline.clinpgxid IS 'The accession ID in ClinPGx for the guideline';


--
-- Name: recommendation; Type: TABLE; Schema: cpic; Owner: -
--

CREATE TABLE cpic.recommendation (
    id integer DEFAULT nextval('cpic.cpic_id'::regclass) NOT NULL,
    guidelineid integer,
    drugid character varying(20),
    implications jsonb,
    drugrecommendation text,
    classification character varying(20),
    phenotypes jsonb,
    activityscore jsonb,
    allelestatus jsonb,
    lookupkey jsonb,
    population text,
    comments text,
    version integer DEFAULT 1,
    dosinginformation boolean DEFAULT false,
    alternatedrugavailable boolean DEFAULT false,
    otherprescribingguidance boolean DEFAULT false
);


--
-- Name: TABLE recommendation; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON TABLE cpic.recommendation IS 'Recommendations for a gene result pulled from a guideline';


--
-- Name: COLUMN recommendation.id; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.recommendation.id IS 'A synthetic numerical ID, auto-assigned, primary key';


--
-- Name: COLUMN recommendation.guidelineid; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.recommendation.guidelineid IS 'The guideline this recommendation appears in';


--
-- Name: COLUMN recommendation.drugid; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.recommendation.drugid IS 'The drug this recommendation is for';


--
-- Name: COLUMN recommendation.implications; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.recommendation.implications IS 'Implications for phenotypic measures, this is a JSON mapping of gene to implication';


--
-- Name: COLUMN recommendation.drugrecommendation; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.recommendation.drugrecommendation IS 'Dosing or therapeutic recommendations, depending on particular drug';


--
-- Name: COLUMN recommendation.classification; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.recommendation.classification IS 'Classification of recommendations, described in supplementary meterial';


--
-- Name: COLUMN recommendation.phenotypes; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.recommendation.phenotypes IS 'Phenotypes that this recommendation applies to, this is a JSON mapping of gene to phenotype';


--
-- Name: COLUMN recommendation.activityscore; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.recommendation.activityscore IS 'Activity score that this recommendation applies to, this is a JSON mapping of gene to score value';


--
-- Name: COLUMN recommendation.allelestatus; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.recommendation.allelestatus IS 'Whether or not an allele is present, used mainly for HLA genes, and used for recommendation lookups. This is a JSON mapping of gene to allele status (positive/negative)';


--
-- Name: COLUMN recommendation.lookupkey; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.recommendation.lookupkey IS 'A key to use for finding a specific recommendation. Made of a JSON object of gene symbol to key value. The key value can be one of phenotype, activity score, or allele status depending on the gene.';


--
-- Name: COLUMN recommendation.population; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.recommendation.population IS 'The population this recommendation is applicable to';


--
-- Name: COLUMN recommendation.comments; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.recommendation.comments IS 'Optional comments about the recommendation';


--
-- Name: COLUMN recommendation.dosinginformation; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.recommendation.dosinginformation IS 'The guideline recommends a dose adjustment based on genetic variants or phenotypes (e.g. "poor metabolizers") as a primary course of action. However, the guideline may also describe extenuating circumstances where this action is not appropriate.';


--
-- Name: COLUMN recommendation.alternatedrugavailable; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.recommendation.alternatedrugavailable IS 'The guideline recommends that an alternate drug be selected for patients based on genetic variants or phenotypes (e.g. "poor metabolizers") as a primary course of action. However, the guideline may also describe extenuating circumstances where this action is not appropriate.';


--
-- Name: COLUMN recommendation.otherprescribingguidance; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.recommendation.otherprescribingguidance IS 'The guideline and other prescribing guidance not described as either dose adjustment or alternate drug.';


--
-- Name: recommendation_view; Type: VIEW; Schema: cpic; Owner: -
--

CREATE VIEW cpic.recommendation_view AS
 SELECT r.id AS recommendationid,
    r.lookupkey,
    d.name AS drugname,
    g.name AS guidelinename,
    g.url AS guidelineurl,
    r.implications,
    r.drugrecommendation,
    r.classification,
    r.phenotypes,
    r.activityscore,
    r.population,
    r.comments
   FROM ((cpic.recommendation r
     JOIN cpic.drug d ON (((r.drugid)::text = (d.drugid)::text)))
     JOIN cpic.guideline g ON ((r.guidelineid = g.id)));


--
-- Name: VIEW recommendation_view; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON VIEW cpic.recommendation_view IS 'A view to help find recommendation data when querying by the lookupKey';


--
-- Name: recommendation_lookup(text); Type: FUNCTION; Schema: cpic; Owner: -
--

CREATE FUNCTION cpic.recommendation_lookup(diplotypelookup text) RETURNS SETOF cpic.recommendation_view
    LANGUAGE sql STABLE SECURITY DEFINER
    AS $$
select * from cpic.recommendation_view where lookupkey <@ (
    select jsonb_object_agg(key, value) as lookupkey
    from (select lookupkey from cpic.diplotype where diplotypekey <@ diplotypelookup::jsonb) x,
        json_each(x.lookupkey)
)
$$;


--
-- Name: FUNCTION recommendation_lookup(diplotypelookup text); Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON FUNCTION cpic.recommendation_lookup(diplotypelookup text) IS 'This function helps translate diplotypes into recommendation data. This relies on the recommendation_view to gather and filter relevant information. The diplotypelookup parameter is a JSON object of gene symbol to JSON allele representation.';


--
-- Name: test_alert; Type: TABLE; Schema: cpic; Owner: -
--

CREATE TABLE cpic.test_alert (
    id integer DEFAULT nextval('cpic.cpic_id'::regclass) NOT NULL,
    population text,
    cdscontext text NOT NULL,
    genes text[],
    phenotype jsonb,
    activityscore jsonb,
    allelestatus jsonb,
    lookupkey jsonb,
    drugid character varying(20),
    alerttext text[] NOT NULL,
    version integer DEFAULT 1
);


--
-- Name: TABLE test_alert; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON TABLE cpic.test_alert IS 'Example CDS test alert language';


--
-- Name: COLUMN test_alert.id; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.test_alert.id IS 'A synthetic numerical ID, primary key';


--
-- Name: COLUMN test_alert.population; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.test_alert.population IS 'The population this test alert is applicable to: general, adult, pediatrics, unspecified';


--
-- Name: COLUMN test_alert.cdscontext; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.test_alert.cdscontext IS 'This should be either "Pre-test", "Post-test" or "No CDS". This field is non-null';


--
-- Name: COLUMN test_alert.genes; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.test_alert.genes IS 'One or more genes this test alert uses for trigger conditions';


--
-- Name: COLUMN test_alert.phenotype; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.test_alert.phenotype IS 'A JSON object of gene symbol keys to phenotype description';


--
-- Name: COLUMN test_alert.activityscore; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.test_alert.activityscore IS 'A JSON object of gene symbol keys to gene activity score';


--
-- Name: COLUMN test_alert.allelestatus; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.test_alert.allelestatus IS 'Whether or not an allele is present, used mainly for HLA genes. This is a JSON mapping of gene to allele status (positive/negative)';


--
-- Name: COLUMN test_alert.lookupkey; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.test_alert.lookupkey IS 'A key to use for finding a specific test alert. Made of a JSON object of gene symbol to key value. The key value can be one of phenotype, activity score, or allele status depending on the gene.';


--
-- Name: COLUMN test_alert.drugid; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.test_alert.drugid IS 'The ID of a drug this alert text is for';


--
-- Name: COLUMN test_alert.alerttext; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.test_alert.alerttext IS 'An array of one or more pieces of alert text';


--
-- Name: test_alert_view; Type: VIEW; Schema: cpic; Owner: -
--

CREATE VIEW cpic.test_alert_view AS
 SELECT t.id AS testalertid,
    t.lookupkey,
    d.name AS drugname,
    t.population,
    t.alerttext,
    t.cdscontext
   FROM (cpic.test_alert t
     JOIN cpic.drug d ON (((t.drugid)::text = (d.drugid)::text)));


--
-- Name: VIEW test_alert_view; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON VIEW cpic.test_alert_view IS 'A view to help find test alert data when querying by the lookupKey';


--
-- Name: test_alert_lookup(text); Type: FUNCTION; Schema: cpic; Owner: -
--

CREATE FUNCTION cpic.test_alert_lookup(lookup text) RETURNS SETOF cpic.test_alert_view
    LANGUAGE sql STABLE SECURITY DEFINER
    AS $$
select * from cpic.test_alert_view where lookupkey <@ (
    select jsonb_object_agg(key, value) as lookupkey
    from (select lookupkey from cpic.diplotype where diplotypekey <@ lookup::jsonb) x,
        json_each(x.lookupkey)
)
$$;


--
-- Name: FUNCTION test_alert_lookup(lookup text); Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON FUNCTION cpic.test_alert_lookup(lookup text) IS 'This function helps translate diplotypes into test alert data. This relies on the test_alert_view to gather and filter relevant information. The lookup parameter is a JSON object of gene symbol to JSON allele representation.';


--
-- Name: allele; Type: TABLE; Schema: cpic; Owner: -
--

CREATE TABLE cpic.allele (
    id integer DEFAULT nextval('cpic.cpic_id'::regclass) NOT NULL,
    version integer DEFAULT 1,
    genesymbol character varying(50) NOT NULL,
    name text NOT NULL,
    functionalstatus text,
    clinicalfunctionalstatus text,
    clinicalfunctionalsubstrate text,
    activityvalue character varying(50),
    definitionid integer NOT NULL,
    citations text[],
    strength text,
    functioncomments text,
    findings text,
    frequency jsonb,
    inferredfrequency boolean DEFAULT false
);


--
-- Name: TABLE allele; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON TABLE cpic.allele IS 'An allele of a gene';


--
-- Name: COLUMN allele.id; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.allele.id IS 'A synthetic numerical ID, auto-assigned, primary key';


--
-- Name: COLUMN allele.version; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.allele.version IS 'The version number, iterates on modification';


--
-- Name: COLUMN allele.genesymbol; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.allele.genesymbol IS 'The HGNC symbol of the gene the allele is for, required';


--
-- Name: COLUMN allele.name; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.allele.name IS 'The name of this allele, required';


--
-- Name: COLUMN allele.functionalstatus; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.allele.functionalstatus IS 'The functional phenotype of this allele';


--
-- Name: COLUMN allele.clinicalfunctionalstatus; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.allele.clinicalfunctionalstatus IS 'The functional phenotype of this allele used for clinical systems';


--
-- Name: COLUMN allele.clinicalfunctionalsubstrate; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.allele.clinicalfunctionalsubstrate IS 'Allele clinical function substrate specificity, optional';


--
-- Name: COLUMN allele.activityvalue; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.allele.activityvalue IS 'Descriptor of activity score, optional';


--
-- Name: COLUMN allele.definitionid; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.allele.definitionid IS 'The reference to the definition for this allele';


--
-- Name: COLUMN allele.citations; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.allele.citations IS 'An array of PubMed IDs use as citations for this functional assignment';


--
-- Name: COLUMN allele.strength; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.allele.strength IS 'The strength of evidence';


--
-- Name: COLUMN allele.functioncomments; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.allele.functioncomments IS 'Comments this functional assignment of this allele';


--
-- Name: COLUMN allele.inferredfrequency; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.allele.inferredfrequency IS 'Indicates (with "true") that the frequencies for this allele have been inferred by an algorithm that aggregates the frequencies for other alleles of this gene and is not based on direct data, defaults to false, should only be 1 per gene';


--
-- Name: allele_definition; Type: TABLE; Schema: cpic; Owner: -
--

CREATE TABLE cpic.allele_definition (
    id integer DEFAULT nextval('cpic.cpic_id'::regclass) NOT NULL,
    version integer DEFAULT 1,
    genesymbol character varying(50) NOT NULL,
    name text NOT NULL,
    pharmvarid character varying(50),
    matchesreferencesequence boolean DEFAULT false,
    structuralvariation boolean DEFAULT false
);


--
-- Name: TABLE allele_definition; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON TABLE cpic.allele_definition IS 'The definition for an allele of a gene';


--
-- Name: COLUMN allele_definition.id; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.allele_definition.id IS 'A synthetic numerical ID, auto-assigned, primary key';


--
-- Name: COLUMN allele_definition.genesymbol; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.allele_definition.genesymbol IS 'The HGNC symbol of the gene the allele is for, required';


--
-- Name: COLUMN allele_definition.name; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.allele_definition.name IS 'The name of this allele, required';


--
-- Name: COLUMN allele_definition.pharmvarid; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.allele_definition.pharmvarid IS 'The PharmVar core allele ID for this allele';


--
-- Name: COLUMN allele_definition.matchesreferencesequence; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.allele_definition.matchesreferencesequence IS 'Indicates (with "true") the variants that define the named allele will match the reference sequence for the gene, defaults to false, should only be 1 per gene';


--
-- Name: COLUMN allele_definition.structuralvariation; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.allele_definition.structuralvariation IS 'Indicates whether this allele definition is a structural variant, default is false. If true, look in the pharmvarid field for the PharmVar ID that defines the structural variation.';


--
-- Name: allele_frequency; Type: TABLE; Schema: cpic; Owner: -
--

CREATE TABLE cpic.allele_frequency (
    alleleid integer NOT NULL,
    population integer NOT NULL,
    frequency numeric,
    label text,
    version integer DEFAULT 1
);


--
-- Name: TABLE allele_frequency; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON TABLE cpic.allele_frequency IS 'A frequency observation for a particular allele in a particular population';


--
-- Name: COLUMN allele_frequency.alleleid; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.allele_frequency.alleleid IS 'The ID of the allele for this observation';


--
-- Name: COLUMN allele_frequency.population; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.allele_frequency.population IS 'The ID of the population for this observation';


--
-- Name: COLUMN allele_frequency.frequency; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.allele_frequency.frequency IS 'The numeric representation of this frequency';


--
-- Name: COLUMN allele_frequency.label; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.allele_frequency.label IS 'The textual label for this frequency, "-" means no observation made';


--
-- Name: COLUMN allele_frequency.version; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.allele_frequency.version IS 'The version number, iterates on modification';


--
-- Name: pair; Type: TABLE; Schema: cpic; Owner: -
--

CREATE TABLE cpic.pair (
    pairid integer DEFAULT nextval('cpic.cpic_id'::regclass) NOT NULL,
    genesymbol character varying(20),
    drugid character varying(20),
    guidelineid integer,
    usedforrecommendation boolean DEFAULT false,
    version integer DEFAULT 1,
    cpiclevel character varying(5) NOT NULL,
    pgkbcalevel character varying(5),
    pgxtesting text,
    citations text[],
    removed boolean DEFAULT false,
    removeddate date,
    removedreason text,
    CONSTRAINT valid_cpiclevel_check CHECK (((cpiclevel)::text = ANY (ARRAY[('A'::character varying)::text, ('A/B'::character varying)::text, ('B'::character varying)::text, ('B/C'::character varying)::text, ('C'::character varying)::text, ('C/D'::character varying)::text, ('D'::character varying)::text]))),
    CONSTRAINT valid_pgkblevel_check CHECK (((pgkbcalevel)::text = ANY (ARRAY[('1A'::character varying)::text, ('1B'::character varying)::text, ('2A'::character varying)::text, ('2B'::character varying)::text, ('3'::character varying)::text, ('4'::character varying)::text]))),
    CONSTRAINT valid_pmids CHECK ((array_to_string(citations, ''::text) ~ '\d+'::text)),
    CONSTRAINT valid_used_check CHECK (((NOT usedforrecommendation) OR (guidelineid IS NOT NULL)))
);


--
-- Name: TABLE pair; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON TABLE cpic.pair IS 'A pair of a gene and a drug that is notable to CPIC';


--
-- Name: COLUMN pair.pairid; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.pair.pairid IS 'A synthetic numerical id, automatically assigned, primary key';


--
-- Name: COLUMN pair.genesymbol; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.pair.genesymbol IS 'The HGNC symbol of the gene in this pair, required';


--
-- Name: COLUMN pair.drugid; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.pair.drugid IS 'The ID of the drug in this pair, required';


--
-- Name: COLUMN pair.guidelineid; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.pair.guidelineid IS 'The ID of a guideline this pair is described in, optional';


--
-- Name: COLUMN pair.usedforrecommendation; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.pair.usedforrecommendation IS 'Whether the gene is used for recommendation lookup for the drug if this pair is part of a guideline, default false';


--
-- Name: COLUMN pair.version; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.pair.version IS 'The version number, iterates on modification';


--
-- Name: COLUMN pair.cpiclevel; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.pair.cpiclevel IS 'The CPIC level of this pair, required';


--
-- Name: COLUMN pair.pgkbcalevel; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.pair.pgkbcalevel IS 'The top level of PharmGKB Clinical Annotation for this pair, optional';


--
-- Name: COLUMN pair.pgxtesting; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.pair.pgxtesting IS 'The top level of PGx testing recommendation from PharmGKB label annotations, optional';


--
-- Name: COLUMN pair.citations; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.pair.citations IS 'The PMID citations in an array for this pair, optional';


--
-- Name: COLUMN pair.removed; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.pair.removed IS 'Has this pair been "removed", eg is no longer a valid pair, default false';


--
-- Name: COLUMN pair.removeddate; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.pair.removeddate IS 'If removed, when was this pair "removed"';


--
-- Name: COLUMN pair.removedreason; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.pair.removedreason IS 'If removed, why was this pair "removed"';


--
-- Name: allele_guideline_view; Type: VIEW; Schema: cpic; Owner: -
--

CREATE VIEW cpic.allele_guideline_view AS
 SELECT DISTINCT a.genesymbol,
    a.name AS allele_name,
    g.name AS guideline_name,
    g.url AS guideline_url
   FROM ((cpic.allele a
     JOIN cpic.pair p ON (((a.genesymbol)::text = (p.genesymbol)::text)))
     JOIN cpic.guideline g ON ((g.id = p.guidelineid)))
  WHERE (a.clinicalfunctionalstatus IS NOT NULL);


--
-- Name: VIEW allele_guideline_view; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON VIEW cpic.allele_guideline_view IS 'A combination of alleles and the guidelines they appear in';


--
-- Name: COLUMN allele_guideline_view.genesymbol; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.allele_guideline_view.genesymbol IS 'The HGNC symbol of the gene';


--
-- Name: COLUMN allele_guideline_view.allele_name; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.allele_guideline_view.allele_name IS 'The name of the allele';


--
-- Name: COLUMN allele_guideline_view.guideline_name; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.allele_guideline_view.guideline_name IS 'The name of the guideline this allele appears in';


--
-- Name: COLUMN allele_guideline_view.guideline_url; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.allele_guideline_view.guideline_url IS 'The URL to the guideline';


--
-- Name: allele_location_value; Type: TABLE; Schema: cpic; Owner: -
--

CREATE TABLE cpic.allele_location_value (
    alleledefinitionid integer NOT NULL,
    locationid integer NOT NULL,
    variantallele text NOT NULL,
    version integer DEFAULT 1
);


--
-- Name: TABLE allele_location_value; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON TABLE cpic.allele_location_value IS 'The change at a specific location for a specific allele';


--
-- Name: COLUMN allele_location_value.alleledefinitionid; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.allele_location_value.alleledefinitionid IS 'The reference to the allele this variant is on';


--
-- Name: COLUMN allele_location_value.locationid; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.allele_location_value.locationid IS 'The reference to the location this variant is for';


--
-- Name: COLUMN allele_location_value.variantallele; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.allele_location_value.variantallele IS 'The allele of this location for the allele';


--
-- Name: COLUMN allele_location_value.version; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.allele_location_value.version IS 'The version number, iterates on modification';


--
-- Name: change_log; Type: TABLE; Schema: cpic; Owner: -
--

CREATE TABLE cpic.change_log (
    date date NOT NULL,
    type text NOT NULL,
    entityid text,
    note text NOT NULL,
    version integer DEFAULT 1,
    deployedrelease text
);


--
-- Name: TABLE change_log; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON TABLE cpic.change_log IS 'A dated freeform text description of a change made to a type of information and optionally for a specific entity';


--
-- Name: COLUMN change_log.date; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.change_log.date IS 'The date the log note is applicable';


--
-- Name: COLUMN change_log.type; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.change_log.type IS 'The type of data this log message is about';


--
-- Name: COLUMN change_log.entityid; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.change_log.entityid IS 'Optional, the specific entity this note is about. For example, could be a gene symbol or drug ID';


--
-- Name: COLUMN change_log.note; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.change_log.note IS 'The freeform text note about what the change was';


--
-- Name: COLUMN change_log.version; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.change_log.version IS 'The version number, iterates on modification';


--
-- Name: COLUMN change_log.deployedrelease; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.change_log.deployedrelease IS 'The release this change was deployed with';


--
-- Name: gene; Type: TABLE; Schema: cpic; Owner: -
--

CREATE TABLE cpic.gene (
    symbol character varying(20) NOT NULL,
    chr character varying(20),
    genesequenceid text,
    proteinsequenceid text,
    chromosequenceid text,
    mrnasequenceid text,
    hgncid text,
    ncbiid text,
    ensemblid text,
    pharmgkbid text,
    frequencymethods text,
    lookupmethod text DEFAULT 'PHENOTYPE'::text,
    version integer DEFAULT 1,
    notesondiplotype text,
    url text,
    functionmethods text,
    notesonallelenaming text,
    includephenotypefrequencies boolean DEFAULT true NOT NULL,
    includediplotypefrequencies boolean DEFAULT true NOT NULL,
    CONSTRAINT gene_chr_check CHECK (((chr)::text ~ '^chr\S+$'::text)),
    CONSTRAINT gene_chromosequenceid_check CHECK ((chromosequenceid ~ '^(NC_\S+)?$'::text)),
    CONSTRAINT gene_ensemblid_check CHECK ((ensemblid ~ '^(ENSG\d+)?$'::text)),
    CONSTRAINT gene_genesequenceid_check CHECK ((genesequenceid ~ '^(NG_\S+)?$'::text)),
    CONSTRAINT gene_hgncid_check CHECK ((hgncid ~ '^(HGNC:\d+)?$'::text)),
    CONSTRAINT gene_mrnasequenceid_check CHECK ((mrnasequenceid ~ '^(NM_\S+)?$'::text)),
    CONSTRAINT gene_pharmgkbid_check CHECK ((pharmgkbid ~ '^(PA\d+)?$'::text)),
    CONSTRAINT gene_proteinsequenceid_check CHECK ((proteinsequenceid ~ '^(NP_\S+)?$'::text))
);


--
-- Name: TABLE gene; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON TABLE cpic.gene IS 'Gene information with a primary key of the approved HGNC symbol for the gene. This means any gene used in the table must be approved by HGNC.';


--
-- Name: COLUMN gene.symbol; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.gene.symbol IS 'Approved HGNC symbol, primary key.';


--
-- Name: COLUMN gene.chr; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.gene.chr IS 'Chromosome symbol. In the form chr##, where ## is the number or X/Y.';


--
-- Name: COLUMN gene.genesequenceid; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.gene.genesequenceid IS 'The RefSeq ID for the sequence that represents this gene, starts with "NG_". No version suffix.';


--
-- Name: COLUMN gene.proteinsequenceid; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.gene.proteinsequenceid IS 'The RefSeq ID for the sequence that represents the protein product of this gene, starts with "NP_". No version suffix.';


--
-- Name: COLUMN gene.chromosequenceid; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.gene.chromosequenceid IS 'The RefSeq ID for the sequence that represents the chromosome this gene is on, starts with "NC_". No version suffix.';


--
-- Name: COLUMN gene.mrnasequenceid; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.gene.mrnasequenceid IS 'The RefSeq ID for the sequence that represents the translation of this gene, starts with "NM_". No version suffix.';


--
-- Name: COLUMN gene.hgncid; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.gene.hgncid IS 'The HGNC numerical ID number for this gene prefixed by "HGNC:"';


--
-- Name: COLUMN gene.ncbiid; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.gene.ncbiid IS 'The NCBI Gene (Entrez) ID number for this gene';


--
-- Name: COLUMN gene.ensemblid; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.gene.ensemblid IS 'The Ensembl ID for this gene';


--
-- Name: COLUMN gene.pharmgkbid; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.gene.pharmgkbid IS 'The ID for this gene in PharmGKB.';


--
-- Name: COLUMN gene.frequencymethods; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.gene.frequencymethods IS 'Text documentation of the methods and caveats for allele frequency data';


--
-- Name: COLUMN gene.lookupmethod; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.gene.lookupmethod IS 'The way to lookup information about diplotypes of this gene, should use ACTIVITY_SCORE, PHENOTYPE, or ALLELE_STATUS';


--
-- Name: COLUMN gene.notesondiplotype; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.gene.notesondiplotype IS 'Optional notes about the diplotypes of the gene';


--
-- Name: COLUMN gene.includephenotypefrequencies; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.gene.includephenotypefrequencies IS 'if allele frequencies exist for this gene, whether to calculate and display phenotype-level frequencies. a true value does not imply existence frequency data';


--
-- Name: COLUMN gene.includediplotypefrequencies; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.gene.includediplotypefrequencies IS 'if allele frequencies exist for this gene, whether to calculate and display diplotype-level frequencies. a true value does not imply existence frequency data';


--
-- Name: change_log_view; Type: VIEW; Schema: cpic; Owner: -
--

CREATE VIEW cpic.change_log_view AS
 WITH x AS (
         SELECT gene.symbol AS entityid,
            gene.symbol AS entityname
           FROM cpic.gene
        UNION ALL
         SELECT drug.drugid AS entityid,
            drug.name AS entityname
           FROM cpic.drug
        )
 SELECT l.date,
    l.type,
    x.entityname,
    l.note,
    l.deployedrelease
   FROM (cpic.change_log l
     LEFT JOIN x ON ((l.entityid = (x.entityid)::text)));


--
-- Name: VIEW change_log_view; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON VIEW cpic.change_log_view IS 'This view of the change_log table add the entity name to make it more readable';


--
-- Name: gene_result; Type: TABLE; Schema: cpic; Owner: -
--

CREATE TABLE cpic.gene_result (
    id integer DEFAULT nextval('cpic.cpic_id'::regclass) NOT NULL,
    genesymbol character varying(50) NOT NULL,
    result text NOT NULL,
    activityscore text,
    ehrpriority text,
    consultationtext text,
    version integer DEFAULT 1,
    frequency jsonb
);


--
-- Name: TABLE gene_result; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON TABLE cpic.gene_result IS 'Possible phenotype values for a gene. The gene + phenotype + activity score should be unique.';


--
-- Name: COLUMN gene_result.id; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.gene_result.id IS 'A synthetic numerical ID, auto-assigned, primary key';


--
-- Name: COLUMN gene_result.genesymbol; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.gene_result.genesymbol IS 'The HGNC symbol of the gene in this pair, required';


--
-- Name: COLUMN gene_result.result; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.gene_result.result IS 'The result for a gene, can either be a phenotype or "allele status" depending on the lookup method for the gene (see lookupMethod in gene table), required';


--
-- Name: COLUMN gene_result.activityscore; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.gene_result.activityscore IS 'Activity score, optional';


--
-- Name: COLUMN gene_result.ehrpriority; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.gene_result.ehrpriority IS 'EHR Priority Result, optional';


--
-- Name: COLUMN gene_result.consultationtext; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.gene_result.consultationtext IS 'Consultation (Interpretation) Text Provided with Test Result';


--
-- Name: COLUMN gene_result.frequency; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.gene_result.frequency IS 'JSON map of frequencies for this gene result with keys being biogeographical groups';


--
-- Name: gene_result_diplotype; Type: TABLE; Schema: cpic; Owner: -
--

CREATE TABLE cpic.gene_result_diplotype (
    id integer DEFAULT nextval('cpic.cpic_id'::regclass) NOT NULL,
    functionphenotypeid integer NOT NULL,
    diplotype text NOT NULL,
    diplotypekey jsonb NOT NULL,
    frequency jsonb
);


--
-- Name: TABLE gene_result_diplotype; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON TABLE cpic.gene_result_diplotype IS 'Specific diplotypes that are associated with a gene result. This table is a child of gene_result_lookup and distantly of gene_result';


--
-- Name: COLUMN gene_result_diplotype.id; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.gene_result_diplotype.id IS 'A synthetic numerical ID, auto-assigned, primary key';


--
-- Name: COLUMN gene_result_diplotype.functionphenotypeid; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.gene_result_diplotype.functionphenotypeid IS 'An ID referencing a gene_result_lookup record, required';


--
-- Name: COLUMN gene_result_diplotype.diplotype; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.gene_result_diplotype.diplotype IS 'A diplotype for the gene in the form Allele1/Allele2, required';


--
-- Name: COLUMN gene_result_diplotype.diplotypekey; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.gene_result_diplotype.diplotypekey IS 'A normalized JSON version of the diplotype for use in lookups. Should be an object with the allele names as properties and the counts as the values. Required';


--
-- Name: gene_result_lookup; Type: TABLE; Schema: cpic; Owner: -
--

CREATE TABLE cpic.gene_result_lookup (
    id integer DEFAULT nextval('cpic.cpic_id'::regclass) NOT NULL,
    phenotypeid integer NOT NULL,
    lookupkey jsonb NOT NULL,
    function1 text,
    function2 text,
    activityvalue1 text,
    activityvalue2 text,
    totalactivityscore text,
    description text
);


--
-- Name: TABLE gene_result_lookup; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON TABLE cpic.gene_result_lookup IS 'Gene descriptions that, when combined, link to a gene result. This table is a child of gene_result.';


--
-- Name: COLUMN gene_result_lookup.id; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.gene_result_lookup.id IS 'A synthetic numerical ID, auto-assigned, primary key';


--
-- Name: COLUMN gene_result_lookup.phenotypeid; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.gene_result_lookup.phenotypeid IS 'An ID referencing the gene_result this is associated with, required';


--
-- Name: COLUMN gene_result_lookup.lookupkey; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.gene_result_lookup.lookupkey IS 'A normalized JSON format of the data used to lookup a diplotype. The keys of this field are either the functions, activity scores, or allele statuses depending on what the gene requires. Required.';


--
-- Name: COLUMN gene_result_lookup.function1; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.gene_result_lookup.function1 IS 'The first allele function';


--
-- Name: COLUMN gene_result_lookup.function2; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.gene_result_lookup.function2 IS 'The second allele function';


--
-- Name: COLUMN gene_result_lookup.activityvalue1; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.gene_result_lookup.activityvalue1 IS 'The activity score for the first allele function';


--
-- Name: COLUMN gene_result_lookup.activityvalue2; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.gene_result_lookup.activityvalue2 IS 'The activity score for the second allele function';


--
-- Name: COLUMN gene_result_lookup.totalactivityscore; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.gene_result_lookup.totalactivityscore IS 'The sum activity score for the functions';


--
-- Name: COLUMN gene_result_lookup.description; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.gene_result_lookup.description IS 'A description of the diplotypes associated with this phenotype';


--
-- Name: diplotype; Type: VIEW; Schema: cpic; Owner: -
--

CREATE VIEW cpic.diplotype AS
 SELECT gp.genesymbol,
    d.diplotype,
    pf.function1,
    pf.function2,
    pf.activityvalue1,
    pf.activityvalue2,
    pf.totalactivityscore,
    pf.description,
    d.diplotypekey,
    gp.result AS generesult,
    gp.ehrpriority,
    gp.consultationtext,
    json_build_object(gp.genesymbol,
        CASE
            WHEN (g.lookupmethod = 'ACTIVITY_SCORE'::text) THEN pf.totalactivityscore
            ELSE gp.result
        END) AS lookupkey
   FROM (((cpic.gene_result_diplotype d
     JOIN cpic.gene_result_lookup pf ON ((d.functionphenotypeid = pf.id)))
     JOIN cpic.gene_result gp ON ((pf.phenotypeid = gp.id)))
     JOIN cpic.gene g ON (((gp.genesymbol)::text = (g.symbol)::text)));


--
-- Name: VIEW diplotype; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON VIEW cpic.diplotype IS 'A combination of gene_result and gene_result_diplotype that allows you to easily query by diplotype and see the phenotype-related data for it';


--
-- Name: COLUMN diplotype.genesymbol; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.diplotype.genesymbol IS 'The HGNC symbol of the gene in this pair, required';


--
-- Name: COLUMN diplotype.diplotype; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.diplotype.diplotype IS 'A diplotype for the gene in the form Allele1/Allele2, required';


--
-- Name: COLUMN diplotype.function1; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.diplotype.function1 IS 'A functional assignment of one of the alleles, optional';


--
-- Name: COLUMN diplotype.function2; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.diplotype.function2 IS 'A functional assignment of one of the alleles, optional';


--
-- Name: COLUMN diplotype.activityvalue1; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.diplotype.activityvalue1 IS 'An activity value assignment of one of the alleles, optional';


--
-- Name: COLUMN diplotype.activityvalue2; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.diplotype.activityvalue2 IS 'An activity value assignment of one of the alleles, optional';


--
-- Name: COLUMN diplotype.totalactivityscore; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.diplotype.totalactivityscore IS 'The total Activity Score number, optional';


--
-- Name: COLUMN diplotype.description; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.diplotype.description IS 'The long-form description of the diplotype';


--
-- Name: COLUMN diplotype.diplotypekey; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.diplotype.diplotypekey IS 'A normalized version of the diplotype that can be used for DB lookups';


--
-- Name: COLUMN diplotype.generesult; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.diplotype.generesult IS 'The result for a gene, can either be a phenotype or "allele status" depending on the lookup method for the gene (see lookupMethod in gene table), required';


--
-- Name: COLUMN diplotype.lookupkey; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.diplotype.lookupkey IS 'A normalized version of the gene phenotype that can be used for recommendation or test alert lookup';


--
-- Name: data_progress; Type: VIEW; Schema: cpic; Owner: -
--

CREATE VIEW cpic.data_progress AS
 SELECT 'Gene'::text AS object_class,
    'Allele Definition Data'::text AS data_type,
    allele_definition.genesymbol AS object_name,
    count(*) AS n
   FROM cpic.allele_definition
  GROUP BY allele_definition.genesymbol
UNION ALL
 SELECT 'Gene'::text AS object_class,
    'Allele Functionality Data'::text AS data_type,
    a.genesymbol AS object_name,
    count(*) AS n
   FROM cpic.allele a
  WHERE (a.clinicalfunctionalstatus IS NOT NULL)
  GROUP BY a.genesymbol
UNION ALL
 SELECT 'Gene'::text AS object_class,
    'Diplotype to Phenotype Data'::text AS data_type,
    diplotype.genesymbol AS object_name,
    count(*) AS n
   FROM cpic.diplotype
  GROUP BY diplotype.genesymbol
UNION ALL
 SELECT 'Gene'::text AS object_class,
    'Frequency Data'::text AS data_type,
    a.genesymbol AS object_name,
    count(*) AS n
   FROM (cpic.allele_frequency f
     JOIN cpic.allele a ON ((f.alleleid = a.id)))
  GROUP BY a.genesymbol
UNION ALL
 SELECT 'Gene'::text AS object_class,
    'Gene CDS Data'::text AS data_type,
    gene_result.genesymbol AS object_name,
    count(*) AS n
   FROM cpic.gene_result
  WHERE (gene_result.consultationtext IS NOT NULL)
  GROUP BY gene_result.genesymbol
UNION ALL
 SELECT 'Gene'::text AS object_class,
    'Gene Phenotype Data'::text AS data_type,
    g.genesymbol AS object_name,
    count(*) AS n
   FROM (cpic.gene_result g
     JOIN cpic.gene_result_lookup pf ON ((g.id = pf.phenotypeid)))
  GROUP BY g.genesymbol
UNION ALL
 SELECT 'Gene'::text AS object_class,
    'PharmVar Allele IDs'::text AS data_type,
    a.genesymbol AS object_name,
    count(*) AS n
   FROM cpic.allele_definition a
  WHERE (a.pharmvarid IS NOT NULL)
  GROUP BY a.genesymbol
UNION ALL
 SELECT 'Drug'::text AS object_class,
    'Flowcharts'::text AS data_type,
    drug.name AS object_name,
    count(*) AS n
   FROM cpic.drug
  WHERE (drug.flowchart IS NOT NULL)
  GROUP BY drug.name
UNION ALL
 SELECT 'Drug'::text AS object_class,
    'Table 2 Recommendations'::text AS data_type,
    d.name AS object_name,
    count(DISTINCT r.id) AS n
   FROM (cpic.recommendation r
     JOIN cpic.drug d ON (((r.drugid)::text = (d.drugid)::text)))
  GROUP BY d.name
UNION ALL
 SELECT 'Drug'::text AS object_class,
    'Drug Test Alerts'::text AS data_type,
    d.name AS object_name,
    count(DISTINCT t.id) AS n
   FROM (cpic.test_alert t
     JOIN cpic.drug d ON (((t.drugid)::text = (d.drugid)::text)))
  GROUP BY d.name
UNION ALL
 SELECT 'Drug'::text AS object_class,
    'Guideline'::text AS data_type,
    d.name AS object_name,
    count(DISTINCT g.id) AS n
   FROM ((cpic.guideline g
     JOIN cpic.pair p ON ((g.id = p.guidelineid)))
     JOIN cpic.drug d ON (((p.drugid)::text = (d.drugid)::text)))
  GROUP BY d.name;


--
-- Name: file_artifact; Type: TABLE; Schema: cpic; Owner: -
--

CREATE TABLE cpic.file_artifact (
    id integer DEFAULT nextval('cpic.cpic_id'::regclass) NOT NULL,
    entityids text[],
    type text NOT NULL,
    filename text NOT NULL,
    url text
);


--
-- Name: TABLE file_artifact; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON TABLE cpic.file_artifact IS 'File artifact information. Each entry is a different file artifact generated by the system';


--
-- Name: COLUMN file_artifact.id; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.file_artifact.id IS 'A synthetic numerical ID, auto-assigned, primary key';


--
-- Name: COLUMN file_artifact.entityids; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.file_artifact.entityids IS 'The IDs of the entities the file is for, required';


--
-- Name: COLUMN file_artifact.type; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.file_artifact.type IS 'The type of file';


--
-- Name: COLUMN file_artifact.filename; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.file_artifact.filename IS 'The name of the file (no path)';


--
-- Name: COLUMN file_artifact.url; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.file_artifact.url IS 'The permanent URL of the current version of this file';


--
-- Name: file_artifact_history; Type: TABLE; Schema: cpic; Owner: -
--

CREATE TABLE cpic.file_artifact_history (
    id integer DEFAULT nextval('cpic.cpic_id'::regclass) NOT NULL,
    fileid integer NOT NULL,
    source text NOT NULL,
    changedate timestamp without time zone DEFAULT CURRENT_TIMESTAMP NOT NULL,
    changemessage text
);


--
-- Name: TABLE file_artifact_history; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON TABLE cpic.file_artifact_history IS 'History information for a related file artifact';


--
-- Name: COLUMN file_artifact_history.id; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.file_artifact_history.id IS 'A synthetic numerical ID, auto-assigned, primary key';


--
-- Name: COLUMN file_artifact_history.fileid; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.file_artifact_history.fileid IS 'The ID of the related File Artifact';


--
-- Name: COLUMN file_artifact_history.source; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.file_artifact_history.source IS 'Where this history message originated from';


--
-- Name: COLUMN file_artifact_history.changedate; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.file_artifact_history.changedate IS 'The date the change was applied';


--
-- Name: COLUMN file_artifact_history.changemessage; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.file_artifact_history.changemessage IS 'A message describing the change that occurred';


--
-- Name: file_note; Type: TABLE; Schema: cpic; Owner: -
--

CREATE TABLE cpic.file_note (
    type text NOT NULL,
    entityid text,
    note text NOT NULL,
    ordinal integer NOT NULL,
    version integer DEFAULT 1
);


--
-- Name: TABLE file_note; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON TABLE cpic.file_note IS 'An ordered note that should appear with the type of information specified';


--
-- Name: COLUMN file_note.type; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.file_note.type IS 'The type of information this note is about';


--
-- Name: COLUMN file_note.entityid; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.file_note.entityid IS 'Optional, the specific entity this note is about. For example, could be a gene symbol or drug ID';


--
-- Name: COLUMN file_note.note; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.file_note.note IS 'The freeform text note about the type/entity';


--
-- Name: COLUMN file_note.ordinal; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.file_note.ordinal IS 'The index number for ordering notes of a given type/entity';


--
-- Name: COLUMN file_note.version; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.file_note.version IS 'The version number, iterates on modification';


--
-- Name: file_status; Type: VIEW; Schema: cpic; Owner: -
--

CREATE VIEW cpic.file_status AS
 SELECT a.id,
    a.entityids,
    a.type,
    a.filename,
    a.url,
    history.latest_change
   FROM (cpic.file_artifact a
     LEFT JOIN ( SELECT h.fileid,
            max(h.changedate) AS latest_change
           FROM cpic.file_artifact_history h
          GROUP BY h.fileid) history ON ((a.id = history.fileid)))
  ORDER BY a.type, a.filename;


--
-- Name: flyway_schema_history; Type: TABLE; Schema: cpic; Owner: -
--

CREATE TABLE cpic.flyway_schema_history (
    installed_rank integer NOT NULL,
    version character varying(50),
    description character varying(200) NOT NULL,
    type character varying(20) NOT NULL,
    script character varying(1000) NOT NULL,
    checksum integer,
    installed_by character varying(100) NOT NULL,
    installed_on timestamp without time zone DEFAULT now() NOT NULL,
    execution_time integer NOT NULL,
    success boolean NOT NULL
);


--
-- Name: guideline_summary_view; Type: VIEW; Schema: cpic; Owner: -
--

CREATE VIEW cpic.guideline_summary_view AS
 SELECT g.name AS guideline_name,
    g.url AS guideline_url,
    array_agg(DISTINCT d.name) AS drugs,
    jsonb_agg(DISTINCT jsonb_build_object('symbol', p.genesymbol, 'url', (('https://cpicpgx.org/gene/'::text || lower((p.genesymbol)::text)) || '/'::text))) AS genes
   FROM ((cpic.guideline g
     JOIN cpic.pair p ON ((g.id = p.guidelineid)))
     JOIN cpic.drug d ON (((p.drugid)::text = (d.drugid)::text)))
  GROUP BY g.name, g.url;


--
-- Name: VIEW guideline_summary_view; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON VIEW cpic.guideline_summary_view IS 'This view lists guidelines and the genes and drugs that are associated with them';


--
-- Name: COLUMN guideline_summary_view.guideline_name; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.guideline_summary_view.guideline_name IS 'The title of the guideline';


--
-- Name: COLUMN guideline_summary_view.guideline_url; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.guideline_summary_view.guideline_url IS 'The URL of the guideline on the CPIC website';


--
-- Name: COLUMN guideline_summary_view.drugs; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.guideline_summary_view.drugs IS 'An array of drug names associated with this guideline';


--
-- Name: COLUMN guideline_summary_view.genes; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.guideline_summary_view.genes IS 'An array of gene data associated with this guideline, each object will have a symbol and a URL for the gene on the CPIC website';


--
-- Name: pair_view; Type: VIEW; Schema: cpic; Owner: -
--

CREATE VIEW cpic.pair_view AS
 SELECT p.pairid,
    p.drugid,
    d.name AS drugname,
    p.genesymbol,
    g.name AS guidelinename,
    g.url AS guidelineurl,
    p.cpiclevel,
    p.pgkbcalevel,
    p.pgxtesting,
    p.citations AS pmids,
        CASE
            WHEN (p.usedforrecommendation AND (p.guidelineid IS NOT NULL)) THEN 'Yes'::text
            WHEN ((NOT p.usedforrecommendation) AND (p.guidelineid IS NOT NULL)) THEN 'No'::text
            ELSE 'n/a'::text
        END AS usedforrecommendation,
        CASE
            WHEN (p.guidelineid IS NULL) THEN true
            ELSE false
        END AS provisional
   FROM ((cpic.pair p
     JOIN cpic.drug d ON (((p.drugid)::text = (d.drugid)::text)))
     LEFT JOIN cpic.guideline g ON ((p.guidelineid = g.id)))
  WHERE (p.removed IS FALSE);


--
-- Name: VIEW pair_view; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON VIEW cpic.pair_view IS 'This pairs view combines information from the pair, drug, and guideline tables to make a more readable view of pair data. This also limits result to pairs which have NOT been removed.';


--
-- Name: COLUMN pair_view.pairid; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.pair_view.pairid IS 'The primary key ID of this pair';


--
-- Name: COLUMN pair_view.drugid; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.pair_view.drugid IS 'The ID of the drug in the pair';


--
-- Name: COLUMN pair_view.drugname; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.pair_view.drugname IS 'The name of the drug in the pair';


--
-- Name: COLUMN pair_view.genesymbol; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.pair_view.genesymbol IS 'The symbol of the drug in the pair';


--
-- Name: COLUMN pair_view.guidelinename; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.pair_view.guidelinename IS 'The name for the guideline of this pair';


--
-- Name: COLUMN pair_view.guidelineurl; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.pair_view.guidelineurl IS 'The URL for the guideline of this pair';


--
-- Name: COLUMN pair_view.cpiclevel; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.pair_view.cpiclevel IS 'The CPIC-assigned level of the pair';


--
-- Name: COLUMN pair_view.pgkbcalevel; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.pair_view.pgkbcalevel IS 'The top level of PharmGKB Clinical Annotation of the pair';


--
-- Name: COLUMN pair_view.pgxtesting; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.pair_view.pgxtesting IS 'The testing level of the label annotation from PharmGKB for this pair';


--
-- Name: COLUMN pair_view.pmids; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.pair_view.pmids IS 'The PMIDs for guideline publications of this pair';


--
-- Name: COLUMN pair_view.provisional; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.pair_view.provisional IS 'The CPIC level assigned to this pair is provisional, true if this pair is not part of a guideline';


--
-- Name: population; Type: TABLE; Schema: cpic; Owner: -
--

CREATE TABLE cpic.population (
    id integer DEFAULT nextval('cpic.cpic_id'::regclass) NOT NULL,
    publicationid integer,
    ethnicity text NOT NULL,
    population text,
    populationinfo text,
    subjecttype text,
    subjectcount integer DEFAULT 0,
    version integer DEFAULT 1
);


--
-- Name: TABLE population; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON TABLE cpic.population IS 'A population description of a group of subjects';


--
-- Name: COLUMN population.id; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.population.id IS 'A synthetic primary key ID';


--
-- Name: COLUMN population.publicationid; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.population.publicationid IS 'A reference to a publication';


--
-- Name: COLUMN population.ethnicity; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.population.ethnicity IS 'The major ethnicity grouping of this population';


--
-- Name: COLUMN population.population; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.population.population IS 'The descriptive name of this population, optional';


--
-- Name: COLUMN population.populationinfo; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.population.populationinfo IS 'Further information about this population, optional';


--
-- Name: COLUMN population.subjecttype; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.population.subjecttype IS 'Information about the types of subjects in this population';


--
-- Name: COLUMN population.subjectcount; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.population.subjectcount IS 'The total number of subjects in this population';


--
-- Name: COLUMN population.version; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.population.version IS 'The version number, iterates on modification';


--
-- Name: population_frequency_view; Type: VIEW; Schema: cpic; Owner: -
--

CREATE VIEW cpic.population_frequency_view AS
 WITH x AS (
         SELECT a.id AS alleleid,
            a.genesymbol,
            a.name,
            f.key AS population_group,
                CASE
                    WHEN (jsonb_typeof(f.value) = 'null'::text) THEN NULL::numeric
                    ELSE (f.value)::numeric
                END AS freq_weighted_avg
           FROM (cpic.allele a
             CROSS JOIN LATERAL jsonb_each(a.frequency) f(key, value))
        ), y AS (
         SELECT f.alleleid,
            p.ethnicity,
            max(f.frequency) AS freq_max,
            min(f.frequency) AS freq_min,
            avg(f.frequency) AS freq_avg,
            sum(p.subjectcount) AS subjectcount
           FROM (cpic.population p
             JOIN cpic.allele_frequency f ON ((p.id = f.population)))
          GROUP BY f.alleleid, p.ethnicity
        )
 SELECT x.genesymbol,
    x.name,
    x.population_group,
    y.subjectcount,
    x.freq_weighted_avg,
    y.freq_avg,
    y.freq_max,
    y.freq_min
   FROM (x
     JOIN y ON (((x.alleleid = y.alleleid) AND (x.population_group = y.ethnicity))));


--
-- Name: VIEW population_frequency_view; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON VIEW cpic.population_frequency_view IS 'A summary of frequency data by allele and major population group';


--
-- Name: COLUMN population_frequency_view.genesymbol; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.population_frequency_view.genesymbol IS 'The HGNC symbol of the gene';


--
-- Name: COLUMN population_frequency_view.name; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.population_frequency_view.name IS 'The allele name';


--
-- Name: COLUMN population_frequency_view.population_group; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.population_frequency_view.population_group IS 'The major grouping of population';


--
-- Name: COLUMN population_frequency_view.subjectcount; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.population_frequency_view.subjectcount IS 'The count of subjects assigned the population group for the given allele';


--
-- Name: COLUMN population_frequency_view.freq_weighted_avg; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.population_frequency_view.freq_weighted_avg IS 'The average frequency weighted by total subjects';


--
-- Name: COLUMN population_frequency_view.freq_avg; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.population_frequency_view.freq_avg IS 'The unweighted average frequency (use with caution)';


--
-- Name: COLUMN population_frequency_view.freq_max; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.population_frequency_view.freq_max IS 'The maximum frequency observed';


--
-- Name: COLUMN population_frequency_view.freq_min; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.population_frequency_view.freq_min IS 'The minimum frequency observed';


--
-- Name: publication; Type: TABLE; Schema: cpic; Owner: -
--

CREATE TABLE cpic.publication (
    id integer DEFAULT nextval('cpic.cpic_id'::regclass) NOT NULL,
    guidelineid integer,
    title text,
    authors text[],
    journal text,
    month integer,
    page character varying(50),
    volume character varying(50),
    year integer,
    pmid text,
    pmcid text,
    doi text,
    url text,
    version integer DEFAULT 1,
    highlightedonsite boolean DEFAULT false,
    fulltextfile text
);


--
-- Name: TABLE publication; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON TABLE cpic.publication IS 'Documents published to an external resource';


--
-- Name: COLUMN publication.id; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.publication.id IS 'A synthetic numerical ID, auto-assigned, primary key';


--
-- Name: COLUMN publication.guidelineid; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.publication.guidelineid IS 'The ID for the guideline this publication is about, optional';


--
-- Name: COLUMN publication.pmid; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.publication.pmid IS 'The PubMed identifier for this publication';


--
-- Name: COLUMN publication.pmcid; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.publication.pmcid IS 'The PubMed Central identifier for this publication';


--
-- Name: COLUMN publication.doi; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.publication.doi IS 'The Document Object Identifier (DOI) for this publication';


--
-- Name: COLUMN publication.url; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.publication.url IS 'The URL for this publication';


--
-- Name: COLUMN publication.highlightedonsite; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.publication.highlightedonsite IS 'true means this publication will show in the CPIC site Publications page, defaults to false';


--
-- Name: COLUMN publication.fulltextfile; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.publication.fulltextfile IS 'publicly-accessible URL to full text of publication';


--
-- Name: publication_supplement; Type: TABLE; Schema: cpic; Owner: -
--

CREATE TABLE cpic.publication_supplement (
    id integer DEFAULT nextval('cpic.cpic_id'::regclass) NOT NULL,
    publicationid integer NOT NULL,
    description text,
    url text NOT NULL,
    version integer DEFAULT 1
);


--
-- Name: TABLE publication_supplement; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON TABLE cpic.publication_supplement IS 'A table to hold optional supplemental files for publications';


--
-- Name: COLUMN publication_supplement.id; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.publication_supplement.id IS 'A synthetic numerical ID, primary key';


--
-- Name: COLUMN publication_supplement.publicationid; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.publication_supplement.publicationid IS 'A foreign-key reference to the publication this is a supplement for';


--
-- Name: COLUMN publication_supplement.description; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.publication_supplement.description IS 'An optional free text description of the supplemental file';


--
-- Name: COLUMN publication_supplement.url; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.publication_supplement.url IS 'The publicly-accessible URL to the supplemental file';


--
-- Name: COLUMN publication_supplement.version; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.publication_supplement.version IS 'The version number, iterates on modification';


--
-- Name: recommendation_alleles_view; Type: VIEW; Schema: cpic; Owner: -
--

CREATE VIEW cpic.recommendation_alleles_view AS
 SELECT a.genesymbol,
    g.chr,
    g.lookupmethod,
    array_agg(DISTINCT a.name ORDER BY a.name) AS alleles,
    count(DISTINCT a.name) AS allele_count
   FROM (cpic.allele a
     JOIN cpic.gene g ON (((a.genesymbol)::text = (g.symbol)::text)))
  WHERE ((a.clinicalfunctionalstatus IS NOT NULL) AND (g.lookupmethod <> 'ALLELE_STATUS'::text))
  GROUP BY a.genesymbol, g.chr, g.lookupmethod
UNION
 SELECT g.symbol AS genesymbol,
    g.chr,
    g.lookupmethod,
    array_agg(DISTINCT a.value ORDER BY a.value) AS alleles,
    count(DISTINCT a.value) AS allele_count
   FROM (cpic.recommendation r
     JOIN cpic.drug d ON (((r.drugid)::text = (d.drugid)::text))),
    (LATERAL jsonb_each_text(r.lookupkey) a(key, value)
     JOIN cpic.gene g ON ((a.key = (g.symbol)::text)))
  WHERE ((r.allelestatus IS NOT NULL) AND (g.lookupmethod = 'ALLELE_STATUS'::text) AND (upper(a.value) !~~ '%NO%RESULT%'::text))
  GROUP BY g.symbol, g.chr, g.lookupmethod;


--
-- Name: VIEW recommendation_alleles_view; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON VIEW cpic.recommendation_alleles_view IS 'A list of genes that are used for recommendation lookup and the alleles to use for those lookups';


--
-- Name: sequence_location; Type: TABLE; Schema: cpic; Owner: -
--

CREATE TABLE cpic.sequence_location (
    id integer DEFAULT nextval('cpic.cpic_id'::regclass) NOT NULL,
    version integer DEFAULT 1,
    name text,
    chromosomelocation text,
    genelocation text,
    proteinlocation text,
    genesymbol character varying(50) NOT NULL,
    dbsnpid text,
    "position" integer,
    CONSTRAINT chromosomelocation_nn CHECK ((chromosomelocation IS NOT NULL)),
    CONSTRAINT position_nn CHECK (("position" IS NOT NULL))
);


--
-- Name: TABLE sequence_location; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON TABLE cpic.sequence_location IS 'A location on a sequence';


--
-- Name: COLUMN sequence_location.name; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.sequence_location.name IS 'The short name of this sequence location, arbitrary but often the gene location and nucleotide change';


--
-- Name: COLUMN sequence_location.chromosomelocation; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.sequence_location.chromosomelocation IS 'The partial HGVS representation of the location on the chromosomal sequence';


--
-- Name: COLUMN sequence_location.genelocation; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.sequence_location.genelocation IS 'The partial HGVS representation of the location on the gene sequence';


--
-- Name: COLUMN sequence_location.proteinlocation; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.sequence_location.proteinlocation IS 'The partial HGVS representation of the location on the protein sequence';


--
-- Name: COLUMN sequence_location.genesymbol; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.sequence_location.genesymbol IS 'The HGNC symbol fo the gene this squence location falls in';


--
-- Name: COLUMN sequence_location.dbsnpid; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.sequence_location.dbsnpid IS 'The DBSNP identifier (rs#) for this location, optional';


--
-- Name: COLUMN sequence_location."position"; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.sequence_location."position" IS 'The position, or starting position, of this variation on the chromosomal/mitochondrial sequence';


--
-- Name: statistic; Type: TABLE; Schema: cpic; Owner: -
--

CREATE TABLE cpic.statistic (
    createdon timestamp without time zone NOT NULL,
    stattype text NOT NULL,
    statvalue numeric NOT NULL
);


--
-- Name: TABLE statistic; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON TABLE cpic.statistic IS 'A collection of numerical statistics with metadata about this database and other CPIC data';


--
-- Name: term; Type: TABLE; Schema: cpic; Owner: -
--

CREATE TABLE cpic.term (
    id integer DEFAULT nextval('cpic.cpic_id'::regclass) NOT NULL,
    category text NOT NULL,
    term text NOT NULL,
    functionaldef text,
    geneticdef text,
    loinc text,
    version integer DEFAULT 1
);


--
-- Name: TABLE term; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON TABLE cpic.term IS 'Standardized terms for clinical PGx test results';


--
-- Name: COLUMN term.id; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.term.id IS 'A synthetic numerical ID, auto-assigned, primary key';


--
-- Name: COLUMN term.category; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.term.category IS 'Category group this term falls into';


--
-- Name: COLUMN term.term; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.term.term IS 'The term name';


--
-- Name: COLUMN term.functionaldef; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.term.functionaldef IS 'The functional definition of the term';


--
-- Name: COLUMN term.geneticdef; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.term.geneticdef IS 'The genetic definition of the term';


--
-- Name: COLUMN term.loinc; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.term.loinc IS 'The LOINC identifier for the term';


--
-- Data for Name: allele; Type: TABLE DATA; Schema: cpic; Owner: -
--

COPY cpic.allele (id, version, genesymbol, name, functionalstatus, clinicalfunctionalstatus, clinicalfunctionalsubstrate, activityvalue, definitionid, citations, strength, functioncomments, findings, frequency, inferredfrequency) FROM stdin;
777429	344	CYP2B6	*4	Increased function	Increased function	\N	\N	777428	{12642465,14515060,17015050,17235330,21659470,21746968,21821736,21976622,23254426,23399569,25934575,26389554,29637923,30085944,30906561,31324697,32238417,35538637}	Moderate	\N	CYP2B6*4 (c.785A>G, p.K262R) - Increased function: CYB2B6*4 is assigned increased function based on in vivo (heterozygous patients only) and in vitro studies. In clinical studies, CYP2B6*4 heterozygotes had significantly increased metabolism of several substrates such as bupropion (14515060, 29637923), nicotine (17015050) and efavirenz (17235330). Numerically higher methadone clearance was observed in CYP2B6*4 carriers, albeit samples sizes were small (26389554, 35538637). Although two studies did not find increased efavirenz clearance compared to the *1 reference (23399569, 23254426), the experts did not find these results convincing due to the small sample size. Multiple in vitro studies using cDNA expression systems showed that CYP2B6*4 has increased activity compared to the *1 reference towards efavirenz, methadone, bupropion nicotine, artemether and selegiline, (12642465, 21746968, 21821736, 31324697, 32238417). One in vitro study using cDNA expression system showed no difference in activity using bupropion as a probe (21659470), but the experts did not find this evidence convincing. Some studies found CYP2B6*4 had less activity compared to the *1 reference towards ketamine, nicotine, cyclophosphamide and ifosphamide (21821736, 21976622, 25934575, 30085944, 30906561). This discrepancy is probably due to differences in the in vitro expression systems and substrates used. Therefore, consensus among experts was increased function based on moderate evidence, but effects may be substrate-dependent.	{"Latino": 0.10623067, "European": 0.040871028, "Oceanian": 0.0, "East Asian": 0.0841915, "Near Eastern": 0.104, "Central/South Asian": 0.099, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.010298969}	f
778424	325	DPYD	c.1774C>T	No function	No function	\N	0.0	778423	{24648345}	Limited	\N	5-fluorouracil (in vitro)	{"Latino": 0.0, "European": 0.000013284529, "East Asian": 0.0015735973, "Central/South Asian": 0.0, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.0}	f
777557	344	CYP2C19	*13	\N	Normal function	\N	\N	777556	{12464799,21325430,25001882,21692664}	Limited	\N	CYP2C19*13 is assigned normal function based on limited evidence. Three in vitro studies using different cell systems found CYP2C19*13 demonstrated similar enzyme activity compared to wildtype with mephenytoin, omeprazole, clopidogrel and other substrates (12464799, 21325430, 25001882, 21692664). Therefore, consensus among experts was normal function based on limited evidence as it was determined the phenotypes containing this allele would be clinically similar to phenotypes comprising normal function alleles.	{"Latino": 0.004, "American": null, "European": 0.0022364424, "Oceanian": null, "East Asian": 0.00011504832, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.012}	f
777747	344	CYP2C9	*40	Uncertain function	Uncertain function	\N	n/a	777746	{24077631,24118918,25142737,25951663,25144335,25476996,25614704,25832633,25884291,25924705,27163851,28758225,23844998}	Inadequate evidence	\N	CYP2C9*40 is assigned uncertain function due to inadequate evidence in one heterozygous subject and in vitro studies. One subject with CYP2C9 *1/*40 genotype exhibited decreased AUC and half-life but similar oral clearance compared to wildtype subjects based on tolbutamide plasma concentrations after one 500mg dose (25614704). In vitro studies found CYP2C9*40 demonstrated enzyme activity ranging from decreased to increased compared to wildtype with various substrates (24077631, 24118918, 23844998, 25142737, 25144335, 25951663, 25476996, 25832633, 25884291, 25924705, 27163851, 28758225, 25614704). Therefore, consensus among experts was uncertain function due to inadequate evidence.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
777757	344	CYP2C9	*45	No function	No function	\N	0.0	777756	{24077631,24118918,25144335,25951663,25142737,25476996,25614704,25884291,25832633,25924705,27163851,23844998}	Limited	\N	CYP2C9*45 is assigned no function based on limited evidence in one heterozygous patient and in vitro studies. One subject with CYP2C9*1/*45 genotype exhibited nearly twice the AUC and half the oral clearance compared to wildtype subjects based on tolbutamide plasma concentrations after one 500mg dose (25614704). Multiple in vitro studies found CYP2C9*45 demonstrated markedly decreased clearance compared to wildtype with various substrates (24077631, 24118918, 25144335, 25951663, 25476996, 25832633, 25924705, 27163851, 23844998, 25614704). Although two in vitro studies showed CYP2C9*45 had similar or increased activity compared to wildtype, the experts did not find these results convincing as in these studies CYP2C9*3 which definitively has no function, demonstrated increased or similar activity compared to wildtype in these studies (25142737, 25884291). Therefore, consensus among experts was no function with an activity value of 0 based on limited evidence as it was determined the phenotypes containing this allele would be clinically distinct from phenotypes comprising normal function or decreased function alleles.	{"Latino": 0.00050, "American": null, "European": 0.00020, "Oceanian": null, "East Asian": null, "Near Eastern": 0.0, "Central/South Asian": 0.00020, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
777376	210	CFTR	S1255P	\N	ivacaftor responsive	\N	\N	777375	{}	\N	\N	\N	\N	f
777378	210	CFTR	S549N	\N	ivacaftor responsive	\N	\N	777377	{}	\N	\N	\N	\N	f
777382	210	CFTR	S549R(T>G)	\N	ivacaftor responsive	\N	\N	777381	{}	\N	\N	\N	\N	f
777384	210	CFTR	S945L	\N	ivacaftor responsive	\N	\N	777383	{}	\N	\N	\N	\N	f
777386	210	CFTR	S977F	\N	ivacaftor responsive	\N	\N	777385	{}	\N	\N	\N	\N	f
6355396	9	CFTR	T1053I	\N	ivacaftor responsive	\N	\N	6355395	{}	\N	\N	\N	\N	f
6355394	9	CFTR	T338I	\N	ivacaftor responsive	\N	\N	6355393	{}	\N	\N	\N	\N	f
6355398	9	CFTR	V232D	\N	ivacaftor responsive	\N	\N	6355397	{}	\N	\N	\N	\N	f
6355400	9	CFTR	V562I	\N	ivacaftor responsive	\N	\N	6355399	{}	\N	\N	\N	\N	f
6355402	9	CFTR	V754M	\N	ivacaftor responsive	\N	\N	6355401	{}	\N	\N	\N	\N	f
779085	115	NUDT15	*11	\N	\N	\N	\N	779084	\N	\N	\N	\N	\N	f
779087	115	NUDT15	*12	\N	\N	\N	\N	779086	\N	\N	\N	\N	\N	f
777699	344	CYP2C9	*16	Decreased function	Decreased function	\N	0.5	777698	{16099926,24077631,24118918,24464553,25142737,25951663,25144335,25476996,25614704,25832633,25884291,25924705,27163851,23844998}	Limited	\N	CYP2C9*16 is assigned decreased function based on limited evidence in a heterozygous patient and in vitro studies. One subject with CYP2C9*1/*16 genotype exhibited decreased clearance compared to wildtype subjects based on tolbutamide plasma concentrations after one 500mg dose. This result correlated with the in vitro study where CYP2C9*16 demonstrated similar enzyme expression but 3.4% enzyme activity with a tolbutamide substrate compared to wildtype (25614704). Multiple in vitro studies similarly found CYP2C9*16 demonstrated decreased clearance with various substrates compared to wildtype (16099926, 24077631, 24118918, 24464553, 25951663, 25144335, 25476996, 25832633, 25884291, 25924705, 27163851, 23844998). Although one in vitro study showed CYP2C9*16 had similar activity compared to wildtype, the experts did not find this result convincing as in this study CYP2C9*2 and CYP2C9*3 which definitively have decreased function and no function, respectively, demonstrated increased activity compared to wildtype (25142737). Therefore, consensus among experts was decreased function with an activity value of 0.5 based on limited evidence as it was determined the phenotypes containing this allele would be clinically distinct from phenotypes comprising normal function alleles.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": 0.001877621, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
777991	340	CYP2D6	*29	\N	Decreased function	\N	0.5	777990	{11470994,11823760,24647041,30366777}	Moderate	\N	CYP2D6*29 is assigned decreased function based on moderate evidence in homozygous subjects and in vitro studies. Three subjects with CYP2D6*29/*29 genotype demonstrated decreased metabolism compared to CYP2D6*1/*29 subjects with a debrisoquine substrate (11470994). Similarly, four subjects with CYP2D6*29/*29 genotype demonstrated decreased metabolism compared to wildtype with dextromethorphan and metoprolol substrates (11823760). Multiple in vitro studies found CYP2D6*29 had decreased enzyme activity compared to wildtype with various substrates (11470994, 24647041, 30366777). Although one study found subjects with CYP2D6*29/*29 genotype demonstrated similar metabolism compared to wildtype with debrisoquine and codeine substrates (11823760) the experts did not find this result convincing due to the small sample size. Therefore, consensus among experts with decreased function with an activity value of 0.5 based on moderate evidence.	{"Latino": 0.0152478125, "American": 0.0020174354, "European": 0.0010464214, "Oceanian": 0.0, "East Asian": 0.000097904944, "Near Eastern": 0.0077560195, "Central/South Asian": 0.0016065163, "Sub-Saharan African": 0.10825595, "African American/Afro-Caribbean": 0.08743822}	f
778003	340	CYP2D6	*35	\N	Normal function	\N	1.0	778002	{9241659,12766015,21833166,24647041,30366777}	Moderate	\N	CYP2D6*35 is assigned normal function based on moderate evidence in heterozygous subjects. CYP2D6*35 was first identified in a subject with CYP2D6*5/*35 genotype demonstrating similar dextromethorphan metabolism compared to CYP2D6 *1/*5 subjects, indicating normal function of the CYP2D6*35 allele (9241659). Similarly, a subject with CYP2D6*4/*35 genotype demonstrated decreased dextromethorphan metabolism compared to wildtype subjects (21833166). Additionally, a study of 396 subjects found the -1584C>G substitution, which is found in CYP2D6*35 and other normal function alleles such as CYP2D6*2, was not observed in any subject demonstrating poor dextromethorphan metabolism, indicating normal function of the CYP2D6*35 allele (12766015). Although two in vitro studies found CYP2D6*35 had decreased enzyme activity compared to wildtype (24647041, 30366777), experts did not find these results convincing as the expression system may not be reflective of in vivo environment as demonstrated by the numerous subjects carrying the CYP2D6*35 allele with substrate metabolism similar to that of wildtype as described previously. Therefore, consensus among experts was normal function with an activity value of 1 based on moderate evidence.	{"Latino": 0.026583293, "American": 0.011335291, "European": 0.05468046, "Oceanian": 0.003691906, "East Asian": 0.0005036332, "Near Eastern": 0.022185262, "Central/South Asian": 0.008267974, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.008867127}	f
778739	296	G6PD	Bao Loc	II/Deficient	II/Deficient	\N	\N	778738	{22293322,17726510}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
779039	296	G6PD	Brighton	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	779038	{22293322}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
779437	322	TPMT	*21	\N	Uncertain function	\N	\N	779436	{18708949,18602085,16917910}	\N	\N	\N	{"Latino": 0.0, "European": 0.00005822823, "East Asian": 0.0, "Near Eastern": null, "Central/South Asian": 0.0, "Sub-Saharan African": null, "African American/Afro-Caribbean": 0.0}	f
779445	322	TPMT	*25	\N	Uncertain function	\N	\N	779444	{18602085}	\N	\N	\N	{"Latino": null, "European": 0.00010, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": 0.0}	f
777981	340	CYP2D6	*24	\N	Uncertain function	\N	n/a	777980	{18838503,24647041,30366777}	Inadequate	\N	CYP2D6*24 is assigned uncertain function due to inadequate evidence. In vitro studies found CYP2D6*24 demonstrated enzyme activity ranging from increased to decreased activity compared to wildtype with various substrates (18838503, 24647041, 30366777). Therefore, consensus among experts was uncertain function.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": 0.0, "Near Eastern": 0.0, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": 0.0}	f
778115	340	CYP2D6	*98	\N	Uncertain function	\N	n/a	778114	{25469868,26310775,26666748,26544071,26406933,27109434,27097346,27016952,26542054,26937172,26968424,27203132,27251229,27354764,27538917}	Inadequate	\N	CYP2D6*98 is assigned uncertain function due to inadequate evidence. In vitro studies found CYP2D6*98 demonstrated enzyme activity ranging from similar to decreased activity compared to wildtype with various substrates (25469868, 26310775, 26666748, 26544071, 26406933, 27109434, 27097346, 27016952, 26542054, 26937172, 26968424, 27203132, 27251229, 27354764, 27538917). Therefore, consensus among experts was uncertain function.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778183	339	CYP2D6	*132	\N	Decreased function	\N	0.25	778182	{32759992}	Limited	\N	CYP2D6*132 is assigned decreased function with an activity value of 0.25 due to limited literature describing function of this allele. One in vitro study demonstrated substantially decreased intrinsic clearance CLint (Vmax/Km) of 3.8% and 0.5% compared to *1 for tamoxifen N-desmethylation and dextromethorphan O-demethylation, respectively (32759992). The allele contains 100C>T and 4181G>C (present in *10) and 2819A>G. There are no data describing the consequence of 2819A>G; however, based on the function of *10 and the in vivo study, consensus among experts was decreased function due to limited evidence.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
3685723	135	RYR1	c.8327C>T	Likely Benign	Normal function	\N	n/a	3685722	{35849058}	\N	\N	BS1	{"Latino": null, "American": null, "European": 0.0014621994, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": 0.0001448}	f
777493	344	CYP2B6	*37	Decreased or no function	Decreased function	\N	\N	777492	{23418033,30201214,18171905,24260284}	Limited	\N	CYP2B6*37 (c.516G>T, p.Q172H/splice defect; c.548T>G, p.V183G; c.785A>G, p.K262R) – Decreased function: CYB2B6*37 is assigned decreased function. CYP2B6*37 contains c.516G>T which causes aberrant splicing (see CYP2B6*6 for more information) (23418033). Multiple in vitro studies using cDNA expression systems found that CYP2B6*37 has no enzyme activity with bupropion and efavirenz compared to the *1 reference (23418033, 30201214). However, there was no in vivo data or data for liver microsomes. As is the same for *6, the mechanism for decreased activity is aberrant splicing caused by c.516G>T, which leads to reduced amounts of protein and thus, activity (14551287, 18171905, 24260284). As a result, alleles having c.516G>T are considered decreased function, regardless of the functional status of additional other variants unless these cause no function (e.g., CYP2B6*13 and CYP2B6*38). Therefore, the consensus among experts was decreased function based on the presence of c.516G>T and limited evidence.	{"Latino": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778428	325	DPYD	c.1777G>A	No function	No function	\N	0.0	778427	{24648345}	Limited	\N	5-fluorouracil (in vitro)	{"Latino": 0.0, "European": 0.00001365011, "East Asian": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
3685743	135	RYR1	c.9268G>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685742	{35849058}	\N	\N	PS4_Sup, BP4	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
779443	322	TPMT	*24	\N	Uncertain function	\N	\N	779442	{18602085,18708949}	\N	\N	\N	{"Latino": 0.001137, "European": 0.000026354577, "East Asian": 0.0, "Near Eastern": null, "Central/South Asian": 0.0, "Sub-Saharan African": null, "African American/Afro-Caribbean": 0.0328}	f
778484	325	DPYD	c.2977C>T	Normal function	Normal function	\N	1.0	778483	{24648345}	Limited	\N	5-fluorouracil (in vitro)	{"Latino": 0.0005154524, "European": 0.0, "East Asian": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.0}	f
778917	296	G6PD	Aachen	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778916	{22293322,10772881,1270075}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322. Originally found in 4 male patients with hemolysis in the same family [PMID1270075], it was reported again in 3 male patients [PMID10772881]. This nucleic acid change results in the same amino acid change as the Loma Linda variant (Asn363Lys).	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
778871	296	G6PD	Viangchan, Jammu	II/Deficient	II/Deficient	\N	\N	778870	{22293322,1805484,3338798}	Moderate	\N	Function assigned based on the WHO recommendations included in PMID 22293322. The presence of this variant in G6PD deficient males (1805484, 3338798) supports this classificaiton.	{"Latino": 0.0, "European": 0.0, "East Asian": 0.002528171, "Central/South Asian": 0.0002621507, "African American/Afro-Caribbean": 0.0}	f
3685587	135	RYR1	c.6847A>C	Variant of uncertain significance	Uncertain function	\N	n/a	3685586	{35849058}	\N	\N	PS4_Sup, PM1, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
779449	322	TPMT	*27	\N	Uncertain function	\N	\N	779448	{19945438}	\N	\N	\N	{"Latino": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
3685621	135	RYR1	c.7085A>G	Variant of uncertain significance	Uncertain function	\N	n/a	3685620	{35849058}	\N	\N	PS4_Sup, PM1_Sup, PM5_Sup, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685871	135	RYR1	c.13505A>G	Variant of uncertain significance	Uncertain function	\N	n/a	3685870	{33767344}	\N	\N	None	{"Latino": null, "American": null, "European": 0.0000588, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": 0.00002413}	f
3685893	135	RYR1	c.14002C>T	Variant of uncertain significance	Uncertain function	\N	n/a	3685892	{35849058}	\N	\N	PM1_Sup, PP3_Mod	{"Latino": null, "American": null, "European": 0.00009414, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
779427	322	TPMT	*16	\N	Uncertain function	\N	\N	779426	{18708949,15652243,25564374,15226673}	\N	\N	\N	{"Latino": 0.00005819, "European": 0.0010142878, "East Asian": 0.00020803267, "Near Eastern": null, "Central/South Asian": 0.0005212, "Sub-Saharan African": null, "African American/Afro-Caribbean": 0.0}	f
779429	322	TPMT	*17	\N	Uncertain function	\N	\N	779428	{18708949,15226673}	\N	\N	\N	{"Latino": null, "European": 0.00040, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
779435	322	TPMT	*20	\N	Uncertain function	\N	\N	779434	{18708949,16917910}	\N	\N	\N	{"Latino": 0.0, "European": 0.00005133778, "East Asian": 0.0, "Near Eastern": null, "Central/South Asian": 0.0, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
777539	344	CYP2C19	*4	\N	No function	\N	\N	777538	{9435198,21358751}	Limited	\N	CYP2C19*4 is assigned no function based on limited evidence in heterozygous subjects and an in vitro study. Two subjects with CYP2C19 *2/*4 genotype demonstrated decreased mephenytoin metabolism compared to wildtype subjects based on urine metabolite concentrations. This correlated with the in vitro experiment which found CYP2C19*4 protein was not expressed but mRNA levels were similar to wildtype indicating CYP2C19*4, which is defined by a SNP in the initiation codon, is not properly translated (9435198). Thus, the CYP2C19*4 defining SNP would result in a nonfunctional protein, even in the presence of a SNP associated with increased enzyme function (21358751). Therefore, consensus among experts was no function based on limited evidence as it was determined the phenotypes containing this allele would be clinically distinct from phenotypes comprising normal function and decreased function alleles.	{"Latino": 0.0005202914, "American": 0.00001870861, "European": 0.002359747, "Oceanian": null, "East Asian": 0.00017735043, "Near Eastern": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.0}	f
778895	296	G6PD	Chatham	II/Deficient	II/Deficient	\N	\N	778894	{22293322,7959686,3393536}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": 0.0, "European": 0.00006178815, "East Asian": 0.000072196955, "Central/South Asian": 0.0013113035, "African American/Afro-Caribbean": 0.0}	f
778693	296	G6PD	Kamogawa	II/Deficient	II/Deficient	\N	\N	778692	{22293322,9410474}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
779691	283	CYP2D6	*2x2	\N	Increased function	\N	2.0	777938	{7616439,7903454,8764380}	Limited	\N	CYP2D6*2x2 is assigned increased function based on limited evidence. CYP2D6*2x2 was described in a family demonstrating increased enzyme activity based on urine metabolites with a debrisoquine substrate (7903454). Subjects with CYP2D6 gene duplications demonstrated increased enzyme activity with the greatest debrisoquine metabolism among all subjects (7616439, 8764380). Therefore, consensus among experts was increased function with an activity value of 2 based on limited evidence as it was determined the phenotypes containing this allele would be clinically distinct from phenotypes comprising normal function alleles.	{"Latino": 0.011836204, "American": 0.0060559562, "European": 0.008509548, "Oceanian": 0.0, "East Asian": 0.0045895264, "Near Eastern": 0.03314872, "Central/South Asian": 0.0069125737, "Sub-Saharan African": 0.018582173, "African American/Afro-Caribbean": 0.01866399}	f
778723	296	G6PD	Ube Konan	III/Deficient	III/Deficient	\N	\N	778722	{22293322,511159,7440223,20621077}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": 0.00007135976, "European": 0.0, "East Asian": 0.0000674127, "Central/South Asian": 0.0, "African American/Afro-Caribbean": 0.000105235464}	f
779001	296	G6PD	Union,Maewo, Chinese-2, Kalo	II/Deficient	II/Deficient	\N	\N	779000	{22293322,4405605,8447319,1303180,8935319}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": 0.00017860332, "European": 0.000045371227, "East Asian": 0.0006079438, "Central/South Asian": 0.00010502547, "African American/Afro-Caribbean": 0.0004229671}	f
779165	323	RYR1	c.1021G>A	Pathogenic	Malignant Hyperthermia associated	\N	n/a	779164	{33767344}	\N	\N	PS3_Mod, PS4, PM1, PP1_St, PP3_Mod, BS2_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685527	135	RYR1	c.6037A>C	Variant of uncertain significance	Uncertain function	\N	n/a	3685526	{35849058}	\N	\N	PS4_Sup, BP4	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685535	135	RYR1	c.6349G>C	Likely Pathogenic	Malignant Hyperthermia associated	\N	n/a	3685534	{35849058}	\N	\N	PS4_Mod, PM1, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
778951	296	G6PD	Alhambra	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778950	{22293322,5413384,4405605,7803800}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
778843	296	G6PD	Lille	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778842	{22293322,22139979}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
778867	296	G6PD	Osaka	II/Deficient	II/Deficient	\N	\N	778866	{22293322,1945893,11271380}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
778759	296	G6PD	Salerno Pyrgos	III/Deficient	III/Deficient	\N	\N	778758	{22293322,22139979,20621077}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": 0.0, "European": 0.0, "East Asian": 0.0, "Central/South Asian": 0.0, "African American/Afro-Caribbean": 0.0}	f
778913	296	G6PD	Tondela	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778912	{22293322,21397531}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
3685883	135	RYR1	c.13913G>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685882	{35849058}	\N	\N	PM1_Sup, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
778001	340	CYP2D6	*34	\N	Normal function	\N	1.0	778000	{24647041,30366777}	Limited	\N	CYP2D6*34 is assigned normal function based on limited evidence. CYP2D6*34 is defined by a common SNP found in more than 50 different CYP2D6 alleles including CYP2D6*2 which is assigned normal function. An in vitro study found CYP2D6*34 had similar enzyme activity compared to wildtype with dextromethorphan and bufuralol substrates (24647041). Although CYP2D6*34 demonstrated decreased enzyme activity with other substrates (24647041, 30366777), the experts did not find this result convincing that the magnitude of decreased activity was clinically significant. Therefore, consensus among experts was normal function with an activity value of 1 based on limited evidence.	{"Latino": 0.00050, "American": 0.0, "European": 0.010744718, "Oceanian": 0.0018, "East Asian": 0.008890849, "Near Eastern": null, "Central/South Asian": 0.0, "Sub-Saharan African": 0.001, "African American/Afro-Caribbean": 0.0}	f
778025	340	CYP2D6	*46	\N	Normal function	\N	1.0	778024	{15768052,24647041,30366777}	Limited	\N	CYP2D6*46 is assigned normal function based on limited evidence. Subjects carrying the CYP2D6*46 allele demonstrated similar dextromethorphan metabolism and tramadol pharmacokinetics compared to subjects with two functional alleles (15768052). An vitro study found CYP2D6*46 demonstrated similar activity compared to wildtype with dextromethorphan and bufuralol substrates (15768052). Although two in vitro study found CYP2D6*46 demonstrated decreased enzyme activity compared to wildtype with dextromethorphan, bufuralol, and primaquine substrates (24647041, 30366777) the experts did not find this result convincing as CYP2D6*46 demonstrated similar activity compared to wildtype in vivo and in vitro with the same substrates. Therefore, consensus among experts was normal function with an activity value of 1 based on limited evidence.	{"Latino": null, "American": 0.001, "European": 0.0, "Oceanian": null, "East Asian": 0.0, "Near Eastern": 0.003, "Central/South Asian": 0.0, "Sub-Saharan African": 0.004215873, "African American/Afro-Caribbean": 0.010738235}	f
778390	327	DPYD	c.1278G>T	Normal function	Normal function	\N	1.0	778389	{24648345}	Limited	\N	5-fluorouracil (in vitro)	{"Latino": 0.0, "European": 0.000013647595, "East Asian": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778959	296	G6PD	Covao do Lobo	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778958	{22293322,16079115}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
778675	296	G6PD	Gaohe	III/Deficient	III/Deficient	\N	\N	778674	{22293322,1945893}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": 0.0, "European": 0.0, "East Asian": 0.0019558913, "Central/South Asian": 0.0, "African American/Afro-Caribbean": 0.0}	f
779179	323	RYR1	c.1598G>A	Variant of uncertain significance	Uncertain function	\N	n/a	779178	{33767344}	\N	\N	PS3_Mod, PM1	{"Latino": null, "American": null, "European": 0.0001764, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": 0.000628}	f
3685455	135	RYR1	c.2122G>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685454	{33767344}	\N	\N	None	{"Latino": null, "American": null, "European": 0.00094113953, "East Asian": null, "Near Eastern": 0.00346, "Central/South Asian": null, "Sub-Saharan African": 0.0001207}	f
3685579	135	RYR1	c.6742C>T	Variant of uncertain significance	Uncertain function	\N	n/a	3685578	{35849058}	\N	\N	PM1	{"Latino": 0.00006545, "American": null, "European": null, "East Asian": null, "Near Eastern": 0.0002884, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685581	135	RYR1	c.6743G>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685580	{35849058}	\N	\N	PM1	{"Latino": null, "American": null, "European": 0.0000441, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
779089	115	NUDT15	*13	\N	\N	\N	\N	779088	\N	\N	\N	\N	\N	f
778386	327	DPYD	c.1218G>A	Normal function	Normal function	\N	1.0	778385	{24648345}	Moderate	\N	5-fluorouracil (in vitro)	{"Latino": 0.0022634026, "European": 0.0002832076, "East Asian": 0.0, "Central/South Asian": 0.00017881053, "Sub-Saharan African": 0.08245437, "African American/Afro-Caribbean": 0.06372611}	f
778827	296	G6PD	Asahikawa	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778826	{22293322,9192788,6500558}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
777565	344	CYP2C19	*17	\N	Increased function	\N	\N	777564	{16413245,17625515,20083681,17625515,32857933,29325448,29136336,31649299,20083681}	Definitive	\N	CYP2C19*17 is assigned increased function based on strong evidence in homozygous and heterozygous subjects. Subjects with CYP2C19 *1/*17 and CYP2C19 *17/*17 genotype demonstrated increased omeprazole metabolism compared to wildtype subjects based on plasma metabolite measurements. The predicted AUC of omeprazole in CYP2C19*17/*17 patients was 63% of the predicted AUC in wildtype subjects. Additionally, in a separate population, CYP2C19*17/*17 subjects demonstrated increased mephenytoin metabolism compared to wildtype and CYP2C19 *1/*17 subjects. A murine study found increased gene transcription of CYP2C19*17 likely results in the observed increased enzyme activity (16413245). CYP2C19 *17/*17 patients taking escitalopram had 42% serum escitalopram concentrations compared to wildtype (17625515). Also, in adolescents with generalized anxiety disorder, patients with *4/*17 or *17/*17 had lower AUC/CMAX compared to normal (*1/*1) and poor metabolizers and expected differences in the ratios of s-citalopram to its metabolite, desmethylcitalopram (PMID 32857933). Additionally, CYP2C19 *1/*17 and *17/*17 carriers in naturalistically studied depressed adults had 10% and 20% lower serum concentration compared to CYP2C19 NMs (29325448). In healthy adults, *17/*17 was associated with lower sertraline AUC vs normal metabolizers (29136336), although in a separate study involving more than 1200 patients, the CYP2C19*17 allele was associated with 8% lower serum concentration compared to NMs (31649299). CYP2C19 *17/*17 patients taking clopidogrel had lower ADP induced platelet aggregation likely as a result of increased clopidogrel metabolism to its active metabolite compared to wildtype and CYP2C19 *1/*17 patients (20083681). Therefore, consensus among experts was increased function based on strong evidence.	{"Latino": 0.16655846, "American": 0.086080186, "European": 0.2154386, "Oceanian": 0.057, "East Asian": 0.020541333, "Near Eastern": 0.1914227, "Central/South Asian": 0.17077276, "Sub-Saharan African": 0.17333587, "African American/Afro-Caribbean": 0.2072274}	f
3685615	135	RYR1	c.7076G>A	Likely Pathogenic	Malignant Hyperthermia associated	\N	n/a	3685614	{35849058}	\N	\N	PS4_Mod, PM1, PP3_Mod	{"Latino": null, "American": null, "European": 0.00002942, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685337	135	RYR1	c.455C>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685336	{35849058}	\N	\N	PS4_Sup, PM1, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
778203	246	CYP2D6	*142	\N	Uncertain function	\N	n/a	778202	{33998274}	Inadequate	\N	CYP2D6*142 is assigned uncertain function based on inadequate evidence. A subject sequenced as CYP2D6*10/*142 had a risperidone/9-hydroxy-risperidone ratio comparable to subjects with an AS of 0.25, 0.5 or 0.75 (33998274). CYP2D6*142 is a rare allele defined by several SNPs including 100C>T which causes decreased function in other CYP2D6 alleles (e.g. *10). Therefore, consensus among experts was uncertain function.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
2091251	244	CYP2D6	*159	\N	Unknown function	\N	n/a	2091250	{}	No Evidence	\N	CYP2D6*159 is assigned unknown function due to no literature describing function of this allele. CYP2D6*159 is defined by the two SNPs defining the normal function *2 allele and one additional SNP that is not found on any other star allele.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": 0.00052, "African American/Afro-Caribbean": null}	f
778719	296	G6PD	Murcia Oristano	III/Deficient	III/Deficient	\N	\N	778718	{22293322,7577654,20621077}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": 0.00007293148, "European": 0.000010226099, "East Asian": 0.0, "Central/South Asian": 0.0, "African American/Afro-Caribbean": 0.0}	f
778785	296	G6PD	Naone	II/Deficient	II/Deficient	\N	\N	778784	{22293322,11852882}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
778969	296	G6PD	Riverside	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778968	{22293322,2602358}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
778965	296	G6PD	Utrecht	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778964	{22293322,14757426}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
3685549	135	RYR1	c.6488G>C	Likely Pathogenic	Malignant Hyperthermia associated	\N	n/a	3685548	{35849058}	\N	\N	PS4_Mod, PM1_Sup, PM5, PP1, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685561	135	RYR1	c.6612C>G	Likely Pathogenic	Malignant Hyperthermia associated	\N	n/a	3685560	{35849058}	\N	\N	PS4_Mod, PM1, PP1_Supp	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685585	135	RYR1	c.6838G>A	Likely Pathogenic	Malignant Hyperthermia associated	\N	n/a	3685584	{35849058}	\N	\N	PS4_Mod, PM1, PS3_Mod	{"Latino": null, "American": null, "European": 0.00007349, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": 0.00002412}	f
3685595	135	RYR1	c.7025A>G	Likely Benign	Normal function	\N	n/a	3685594	{35849058}	\N	\N	PS3_Mod, PM1, PP1, BS1, BS2	{"Latino": 0.0005235, "American": null, "European": 0.0016278748, "East Asian": null, "Near Eastern": null, "Central/South Asian": 0.001243, "Sub-Saharan African": 0.0004104}	f
3685605	135	RYR1	c.7043A>G	Likely Pathogenic	Malignant Hyperthermia associated	\N	n/a	3685604	{35849058}	\N	\N	PS4_Mod, PM1, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": 0.00004829}	f
779431	322	TPMT	*18	\N	Uncertain function	\N	\N	779430	{18708949,15226673}	\N	\N	\N	{"Latino": 0.0, "European": 0.000011514104, "East Asian": 0.0, "Near Eastern": null, "Central/South Asian": 0.0, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778380	327	DPYD	c.1156G>T (*12)	No function	No function	\N	0.0	778379	{24648345}	Moderate	\N	5-fluorouracil (in vitro)	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
3685523	135	RYR1	c.5441T>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685522	{35849058}	\N	\N	None	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685577	135	RYR1	c.6710G>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685576	{35849058}	\N	\N	PS4_Sup, PM1, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685593	135	RYR1	c.7018T>C	Variant of uncertain significance	Uncertain function	\N	n/a	3685592	{35849058}	\N	\N	PS4_Sup, PM1	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
778129	339	CYP2D6	*105	\N	Unknown function	\N	n/a	778128	{}	No Evidence	\N	CYP2D6*105 is assigned unknown function due to no literature describing function of this allele. Therefore, consensus among experts was unknown function due to no available evidence.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": 0.0, "Near Eastern": 0.006, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778372	327	DPYD	c.1024G>A	No function	No function	\N	0.0	778371	{24648345}	Limited	\N	5-fluorouracil (in vitro)	{"Latino": 0.0, "European": 0.0, "East Asian": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.0031082802}	f
3685937	135	RYR1	c.14524G>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685936	{35849058}	\N	\N	PM1_Sup, PP3_Mod	{"Latino": null, "American": null, "European": 0.0000147, "East Asian": null, "Near Eastern": 0.0008641, "Central/South Asian": 0.000207, "Sub-Saharan African": 0.0002655}	f
778911	296	G6PD	Serres	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778910	{22293322,9674740}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
778773	296	G6PD	Shenzen	II/Deficient	II/Deficient	\N	\N	778772	{22293322,20582980}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
3564277	147	G6PD	Telti, Kobe	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	3564276	{22293322,7327562}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
3685415	135	RYR1	c.1422G>T	Variant of uncertain significance	Uncertain function	\N	n/a	3685414	{35849058}	\N	\N	PM1	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
778374	327	DPYD	c.1057C>T	No function	No function	\N	0.0	778373	{24648345}	Limited	\N	5-fluorouracil (in vitro)	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778376	327	DPYD	c.1108A>G	Normal function	Normal function	\N	1.0	778375	{24648345}	Limited	\N	5-fluorouracil (in vitro)	{"Latino": 0.0, "European": 0.0, "East Asian": 0.0, "Central/South Asian": 0.00028279895, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.0}	f
3942828	114	DPYD	c.1129-5923C>G	Decreased function	Decreased function	\N	0.5	3942827	{28295243}	Strong	\N	5-fluorouracil (ex vivo)	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778422	325	DPYD	c.1682G>T	Normal function	Normal function	\N	1.0	778421	{24648345}	Limited	\N	5-fluorouracil (in vitro)	{"Latino": 0.00010, "European": 0.000013742599, "East Asian": 0.0, "Central/South Asian": 0.00010, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778426	325	DPYD	c.1775G>A	No function	No function	\N	0.0	778425	{24648345}	Limited	\N	5-fluorouracil (in vitro)	{"Latino": 0.0, "European": 0.0, "East Asian": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778993	296	G6PD	S. Antioco	II/Deficient	II/Deficient	\N	\N	778992	{22293322}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
778352	331	DPYD	c.557A>G	Decreased function	Decreased function	\N	0.5	778351	{24648345}	Moderate	\N	5-fluorouracil (in vitro)	{"Latino": 0.0012139219, "European": 0.00008854784, "East Asian": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": 0.025914682, "African American/Afro-Caribbean": 0.01233121}	f
778378	327	DPYD	c.1129-5923C>G, c.1236G>A (HapB3)	Decreased function	Decreased function	\N	0.5	778377	{28295243}	Strong	c.1129-5923C>G is likely HapB3 causal variant. c.1236G>A (E412E) is a proxy SNP for intronic c.1129-5923C>G, which is LD.	5-fluorouracil (ex vivo)	{"Latino": 0.005925072, "European": 0.023735587, "East Asian": 0.0, "Central/South Asian": 0.019658487, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.0031082802}	f
3685807	135	RYR1	c.11416G>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685806	{35849058}	\N	\N	PS4_Sup, PP1, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685815	135	RYR1	c.11748T>G	Variant of uncertain significance	Uncertain function	\N	n/a	3685814	{35849058}	\N	\N	None	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
777481	344	CYP2B6	*31	Normal function	Normal function	\N	\N	777480	{26655325,30201214}	Limited	\N	CYP2B6*31 (c.937C>A, p.L313I) – Normal function: CYP2B6*31 is assigned normal function. A study evaluating efavirenz content in hair samples among patients with HIV taking efavirenz for more than three months found CYP2B6*31 did not impact long term efavirenz content (26655325). An in vitro study using a cDNA expression system similarly found CYP2B6*31 demonstrated similar enzyme activity compared to the *1 reference (30201214). Therefore, consensus among experts was normal function based on limited evidence.	{"Latino": 0.0, "European": 0.000007472868, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": 0.0, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
777785	344	CYP2C9	*59	Decreased function	Uncertain function	\N	n/a	777784	{25142737,25994031,25884291}	Inadequate evidence	\N	CYP2C9*59 is assigned uncertain function due to inadequate evidence. CYP2C9*59 was first described in a patient requiring a low daily warfarin dose of 1.5mg (25994031). No variant was observed in VKORC1 or CYP4F2 in this patient and a subsequent in silico study showed destabilization of the interaction with the heme group may cause reduction in catalytic activity in this allele. In vitro studies found CYP2C9*59 demonstrated decreased enzyme activity with multiple substrates (25142737, 25994031, 25884291). Consensus was not achieved among experts and therefore uncertain function was assigned.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778486	325	DPYD	c.2983G>T (*10)	No function	No function	\N	0.0	778485	{24648345}	Moderate	\N	5-fluorouracil (in vitro)	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778488	325	DPYD	c.3049G>A	Normal function	Normal function	\N	1.0	778487	{24648345}	Limited	\N	5-fluorouracil (in vitro)	{"Latino": 0.0, "European": 0.00001364737, "East Asian": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778855	296	G6PD	Chinese-1	II/Deficient	II/Deficient	\N	\N	778854	{22293322,1459579}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
778737	296	G6PD	Sao Borja	IV/Normal	IV/Normal	\N	\N	778736	{22293322,8436389}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": 0.0, "European": 0.000054038475, "East Asian": 0.0, "Central/South Asian": 0.0, "African American/Afro-Caribbean": 0.0}	f
779227	323	RYR1	c.7523G>A	Likely Pathogenic	Malignant Hyperthermia associated	\N	n/a	779226	{33767344}	\N	\N	PS2_PM6_Sup, PS3_Mod, PS4, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
779005	296	G6PD	Figuera da Foz	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	779004	{22293322,18056001}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
3685703	135	RYR1	c.7816T>A	Likely Benign	Normal function	\N	n/a	3685702	{35849058}	\N	\N	BS2_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685715	135	RYR1	c.8188G>C	Variant of uncertain significance	Uncertain function	\N	n/a	3685714	{35849058}	\N	\N	PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685737	135	RYR1	c.8729C>T	Variant of uncertain significance	Uncertain function	\N	n/a	3685736	{35849058}	\N	\N	PS4_Sup	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685755	135	RYR1	c.9652G>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685754	{35849058}	\N	\N	PS4_Sup	{"Latino": null, "American": null, "European": 0.0000147, "East Asian": 0.0001925, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
779091	115	NUDT15	*14	\N	\N	\N	\N	779090	\N	\N	\N	\N	\N	f
1777311	256	CYP2D6	*4x2	\N	No function	\N	0.0	777942	{10022755,12152006}	Moderate	\N	CYP2D6*4x2 is assigned no function based on moderate evidence. CYP2D6*4x2 has been described in subjects demonstrating decreased metabolism of dextromethorphan or debrisoquine (10022755, 12152006). CYP2D6*4 is defined by a splicing defect resulting in a nonfunctional protein and gene duplication would therefore not impact enzyme activity. Therefore, consensus among experts was no function with an activity value of 0 based on moderate evidence.	{"Latino": 0.0040316023, "American": 0.0010676404, "European": 0.0065507535, "Oceanian": 0.0, "East Asian": 0.0, "Near Eastern": 0.0032411083, "Central/South Asian": 0.00047151276, "Sub-Saharan African": 0.019609926, "African American/Afro-Caribbean": 0.026700884}	f
778689	296	G6PD	Kambos	III/Deficient	III/Deficient	\N	\N	778688	{22293322,15223006}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
777577	344	CYP2C19	*25	\N	Decreased function	\N	\N	777576	{25001882,19636337,31713493}	Limited	\N	CYP2C19*25 is assigned decreased function based on limited in vitro and computational evidence. An in vitro study found CYP2C19*25 had decreased intrinsic clearance compared to wildtype with clopidogrel and mephenytoin, and omeprazole substrates (25001882, 31713493). A computational analysis of the Phe448Leu amino acid substitution in CYP2C19*25 predicted the change as deleterious. An examination of the structure showed the amino acid substitution, which is important for the heme-binding region, could disrupt the hydrophobic pocket in the region (19636337). Therefore, consensus among experts was decreased function based on limited evidence as it was determined the phenotypes containing this allele would be clinically distinct from phenotypes comprising normal function alleles.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": 0.00018712576, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
3685489	135	RYR1	c.4024A>G	Benign	Normal function	\N	n/a	3685488	{33767344}	\N	\N	BA1	{"Latino": 0.01629, "American": null, "European": 0.0005883, "East Asian": null, "Near Eastern": 0.0023787767, "Central/South Asian": 0.001244, "Sub-Saharan African": 0.1514}	f
777805	326	CYP2C9	*69	Uncertain function	Uncertain function	\N	n/a	777804	{33536773}	Inadequate evidence	\N	CYP2C9*69 is assigned uncertain funciton due to inadequate evidence. The nonsynonymous variant present in CYP2C9*69 is predicted to be deleterious in both SIFT and Polyphen predictions. There are no in vitro or clinical studies reported. Consensus was not achieved among experts and therefore uncertain function was assigned.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
1406318	326	CYP2C9	*73	Unknown function	Unknown function	\N	n/a	1406317	{}	No evidence	\N	CYP2C9*73 is assigned unknown function due to no literature describing function of this allele. Therefore, consensus among experts was unknown function due to no available evidence.	{"Latino": 0.0, "American": null, "European": 0.00010, "Oceanian": null, "East Asian": null, "Near Eastern": 0.0, "Central/South Asian": 0.00040, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778775	296	G6PD	Gond	Uncertain	Uncertain function	\N	\N	778774	{22293322,20713184}	Inadequate	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": 0.000035645542, "European": 0.000045109253, "East Asian": 0.0, "Central/South Asian": 0.008700666, "African American/Afro-Caribbean": 0.0}	f
778819	296	G6PD	Harilaou	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778818	{22293322,2222408}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": 0.00003647638, "European": 0.0, "East Asian": 0.0, "Central/South Asian": 0.0, "African American/Afro-Caribbean": 0.0}	f
778987	296	G6PD	Pawnee	II/Deficient	II/Deficient	\N	\N	778986	{22293322,1611091}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
778865	296	G6PD	Piotrkow	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778864	{22293322,18066402}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
3685543	135	RYR1	c.6478G>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685542	{33767344}	\N	\N	PM1	{"Latino": null, "American": null, "European": 0.0000147, "East Asian": 0.0001922, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": 0.0004825}	f
778943	296	G6PD	Praha	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778942	{22293322,7803800}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
778799	296	G6PD	Tsukui	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778798	{22293322,3360447}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
3685479	135	RYR1	c.3224G>A	Likely Benign	Normal function	\N	n/a	3685478	{35849058}	\N	\N	PS4_Sup, BS2_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": 0.00002413}	f
3685571	135	RYR1	c.6640G>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685570	{35849058}	\N	\N	PM1	{"Latino": null, "American": null, "European": 0.0000294, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": 0.0001447}	f
779201	323	RYR1	c.7048G>A	Pathogenic	Malignant Hyperthermia associated	\N	n/a	779200	{33767344}	\N	\N	PS3_Mod, PS4, PM1, PP1_St, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
779441	322	TPMT	*23	\N	No function	\N	\N	779440	{17885628,18708949}	\N	\N	\N	{"Latino": 0.0, "European": 0.000026239319, "East Asian": 0.0, "Near Eastern": null, "Central/South Asian": 0.0, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
3685397	135	RYR1	c.1100G>T	Variant of uncertain significance	Uncertain function	\N	n/a	3685396	{35849058}	\N	\N	PS4_Sup, PM1, PP3_Mod	{"Latino": null, "American": null, "European": 0.0000147, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685417	135	RYR1	c.1453A>G	Variant of uncertain significance	Uncertain function	\N	n/a	3685416	{33767344}	\N	\N	PM1	{"Latino": 0.0003276, "American": null, "European": 0.0005588, "East Asian": 0.0001925, "Near Eastern": 0.003165, "Central/South Asian": null, "Sub-Saharan African": 0.0001933}	f
3685419	135	RYR1	c.1459C>G	Variant of uncertain significance	Uncertain function	\N	n/a	3685418	{35849058}	\N	\N	PS4_Sup, PM1	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685473	135	RYR1	c.3166G>C	Likely Pathogenic	Malignant Hyperthermia associated	\N	n/a	3685472	{35849058}	\N	\N	PS4_Mod, PP1_St	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
779175	323	RYR1	c.1589G>A	Likely Pathogenic	Malignant Hyperthermia associated	\N	n/a	779174	{33767344}	\N	\N	PS4_Mod, PM1, PP3_Mod	{"Latino": null, "American": null, "European": 0.00007351, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685459	135	RYR1	c.2537C>T	Variant of uncertain significance	Uncertain function	\N	n/a	3685458	{35849058}	\N	\N	PS4_Sup	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
777711	344	CYP2C9	*22	Uncertain function	Uncertain function	\N	n/a	777710	{23752738}	Inadequate evidence	\N	CYP2C9*22 is assigned uncertain function due to inadequate evidence. In one in vitro study, CYP2C9*22 demonstrated decreased enzyme activity compared to wildtype with a warfarin and tolbutamide substrate (23752738). Therefore, consensus among experts was uncertain function due to insufficient evidence.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
1777312	256	CYP2D6	*4x≥3	\N	No function	\N	0.0	777942	{10022755,12152006,26602992}	Moderate	\N	CYP2D6*4x≥3 is assigned no function based on moderate evidence. CYP2D6*4x3 was detected in two samples (266029920). CYP2D6*4 duplication has been described in subjects demonstrating decreased metabolism of dextromethorphan or debrisoquine (10022755, 12152006). CYP2D6*4 is defined by a splicing defect resulting in a nonfunctional protein and gene duplication or multiplications would therefore not impact enzyme activity. Therefore, consensus among experts was no function with an activity value of 0 based on moderate evidence.	{"Latino": null, "American": 0.0, "European": 0.0, "Oceanian": null, "East Asian": 0.0, "Near Eastern": null, "Central/South Asian": 0.0, "Sub-Saharan African": 0.001, "African American/Afro-Caribbean": 0.001}	f
778035	340	CYP2D6	*51	\N	No function	\N	0.0	778034	{18784265,24647041,30366777}	Limited	\N	CYP2D6*51 is assigned no function based on limited evidence. Multiple in vitro studies found CYP2D6*51 had nondetectable enzyme activity with multiple substrates (18784265, 24647041, 30366777). Therefore, consensus among experts was no function with an activity value of 0 based on limited evidence.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": 0.00048685525, "Near Eastern": 0.0, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778440	325	DPYD	c.1906A>C	Normal function	Normal function	\N	1.0	778439	{24648345}	Limited	\N	5-fluorouracil (in vitro)	{"Latino": 0.00020, "European": 0.0, "East Asian": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778444	325	DPYD	c.2021G>A	No function	No function	\N	0.0	778443	{24648345}	Limited	\N	5-fluorouracil (in vitro)	{"Latino": 0.0, "European": 0.0, "East Asian": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
779167	323	RYR1	c.1021G>C	Pathogenic	Malignant Hyperthermia associated	\N	n/a	779166	{33767344}	\N	\N	PS1, PS3_Mod, PS4_Mod, PM1_Sup, PP1, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685475	135	RYR1	c.3166G>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685474	{35849058}	\N	\N	PS4_Sup	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685481	135	RYR1	c.3418C>T	Variant of uncertain significance	Uncertain function	\N	n/a	3685480	{35849058}	\N	\N	None	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": 0.00004827}	f
3685487	135	RYR1	c.3667G>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685486	{35849058}	\N	\N	None	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
779193	323	RYR1	c.6617C>G	Pathogenic	Malignant Hyperthermia associated	\N	n/a	779192	{33767344}	\N	\N	PS3_Mod, PS4_Mod, PM1, PP1_Mod, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685613	135	RYR1	c.7073T>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685612	{33767344}	\N	\N	PM1, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685739	135	RYR1	c.8926C>T	Variant of uncertain significance	Uncertain function	\N	n/a	3685738	{35849058}	\N	\N	PS4_Sup, BP4	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685799	135	RYR1	c.11132C>T	Variant of uncertain significance	Uncertain function	\N	n/a	3685798	{35849058}	\N	\N	PS4_Sup, PP1	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
779011	296	G6PD	Cosenza	II/Deficient	II/Deficient	\N	\N	779010	{22293322,7959686,8447319}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": 0.0, "European": 0.000010319598, "East Asian": 0.0, "Central/South Asian": 0.0, "African American/Afro-Caribbean": 0.0}	f
778699	296	G6PD	Costanzo	II/Deficient	II/Deficient	\N	\N	778698	{22293322}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
779326	322	SLCO1B1	*25	\N	Uncertain function	\N	\N	779325	{22147369}	Inadequate	\N	SLCO1B1*25 is assigned uncertain function based on no in vitro evidence and limited clinical data. One clinical study showed no statistical difference in methotrexate clearance for one heterozygous patient (22147369). Therefore, consensus among experts was uncertain function due to inadequate evidence.	{"American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778741	296	G6PD	Crispim	II/Deficient	II/Deficient	\N	\N	778740	{22293322,12367584}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
777485	344	CYP2B6	*33	\N	Uncertain function	\N	\N	777484	{23418033,30201214}	Inadequate	\N	CYP2B6*33 (c.1459C>A, p.R487S) – Uncertain function: CYP2B6*33 is assigned uncertain function. In vitro studies using cDNA expression systems found CYP2B6*33 demonstrated activity similar to the *1 reference or increased enzyme activity (23418033, 30201214). This discrepancy is probably due to differences in the in vitro expression systems and substrates used. Therefore, consensus among experts was uncertain function based on inadequate evidence as it could not be determined if phenotypes containing this allele would be clinically distinct from phenotypes comprising normal function alleles.	{"Latino": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
779344	322	SLCO1B1	*34	\N	Uncertain function	\N	\N	779343	{22147369,33658230}	Inadequate	\N	SLCO1B1*34 is assigned uncertain function based on limited in vitro evidence and clinical data. One clinical study showed no statistical difference in methotrexate clearance (22147369). One in vitro study found normal protein expression and transport (33658230). Therefore, consensus among experts was uncertain function due to inadequate evidence.	{"American": null, "European": 0.0, "Oceanian": null, "East Asian": 0.0, "Near Eastern": null, "Central/South Asian": 0.0, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
777949	340	CYP2D6	*7	\N	No function	\N	0.0	777948	{7845481,24647041,30366777}	Limited	\N	CYP2D6*7 is assigned no function based on limited evidence. CYP2D6*7 was first described in subjects demonstrating decreased sparteine metabolism (7845481). Two in vitro studies found CYP2D6*7 had nondetectable or markedly decreased enzyme activity compared to wildtype with tamoxifen, bufuralol, dextromethorphan, and primaquine substrates (24647041, 30366777). CYP2D6*7 is defined by an amino substitution near the active site disrupting protein folding and resulting in a nonfunctional enzyme based on computational analysis (7845481). Therefore, consensus among experts was no function with an activity value of 0 based on limited evidence as it was determined the phenotypes containing this allele would be clinically distinct from phenotypes comprising normal and decreased function alleles.	{"Latino": 0.0, "American": 0.0030718232, "European": 0.0005116425, "Oceanian": 0.0, "East Asian": 0.000073912495, "Near Eastern": 0.00286119, "Central/South Asian": 0.0073079397, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.0002489224}	f
778454	325	DPYD	c.2279C>T	Decreased function	Decreased function	\N	0.5	778453	{24648345}	Limited	\N	5-fluorouracil (in vitro)	{"Latino": 0.0, "European": 0.0, "East Asian": 0.0, "Central/South Asian": 0.0060296794, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.0}	f
778749	296	G6PD	A- 680T_376G	III/Deficient	III/Deficient	\N	\N	778748	{22293322,32387609,2572288}	strong	\N	Function assigned based on the WHO recommendations included in PMID 22293322. Additional in vitro (32387609) and the presence of this variant in G6PD deficient males (2572288) supports this classificaiton.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
778909	296	G6PD	Iwatsuki	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778908	{22293322,1945893}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
3685441	135	RYR1	c.1615T>G	Likely Pathogenic	Malignant Hyperthermia associated	\N	n/a	3685440	{35849058}	\N	\N	PS4_Mod, PM1_Sup, PM5_Sup, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685801	135	RYR1	c.11266C>G	Benign	Normal function	\N	n/a	3685800	{33767344}	\N	\N	BA1	{"Latino": 0.07252, "American": null, "European": 0.019045949, "East Asian": 0.05963, "Near Eastern": 0.0018488563, "Central/South Asian": 0.03271, "Sub-Saharan African": 0.00777}	f
3685819	135	RYR1	c.11813G>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685818	{35849058}	\N	\N	None	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
779231	323	RYR1	c.11969G>T	Pathogenic	Malignant Hyperthermia associated	\N	n/a	779230	{33767344}	\N	\N	PS3_Mod, PS4, PP1_St	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
777453	344	CYP2B6	*17	Normal function	Normal function	\N	\N	777452	{16272958,26655325,30201214,32238417,35538637}	Limited	\N	CYP2B6*17 (c.76A>T, p.T26S; c.83A>G, p.D28G; c.85C>A+c.86G>C, p.R29T) – Normal function: CYP2B6*17 is assigned normal function. A study evaluating efavirenz content in hair samples among HIV patients taking efavirenz for more than three months found that long term efavirenz exposure was not impacted by the CYP2B6*17 allele (26655325). Additionally, CYP2B6*17 had similar enzyme activity in vitro using cDNA expression systems compared to the *1 reference (16272958, 30201214, 32238417), but decreased activity for methadone (35538637). This discrepancy is probably due to differences in the in vitro expression systems and substrates used. Therefore, consensus among experts was normal function based on limited evidence.	{"Latino": 0.0, "European": 0.0, "Oceanian": null, "East Asian": 0.0, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": 0.0126, "African American/Afro-Caribbean": 0.071}	f
778191	339	CYP2D6	*136	\N	Uncertain function	\N	n/a	778190	{32759992}	Inadequate	\N	CYP2D6*136 is assigned uncertain function due to inadequate literature describing function of this allele. One in vitro study demonstrated substantially decreased intrinsic clearance CLint (Vmax/Km) of 8.9% and 12.7% compared to *1 for tamoxifen N-desmethylation and dextromethorphan O-demethylation, respectively (32759992). Therefore, consensus among experts was uncertain function due to inadequate evidence.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778859	296	G6PD	Bajo Maumere	III/Deficient	III/Deficient	\N	\N	778858	{22293322,16927025}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
3685507	135	RYR1	c.5036G>A	Likely Benign	Normal function	\N	n/a	3685506	{33767344}	\N	\N	PP3_Mod, BS1, BS2_Mod	{"Latino": 0.000327, "American": null, "European": 0.0017036498, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": 0.0001206}	f
3685521	135	RYR1	c.5440A>G	Variant of uncertain significance	Uncertain function	\N	n/a	3685520	{35849058}	\N	\N	PS4_Sup, BP4	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685525	135	RYR1	c.5890C>T	Variant of uncertain significance	Uncertain function	\N	n/a	3685524	{35849058}	\N	\N	BP4	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685829	135	RYR1	c.12028G>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685828	{35849058}	\N	\N	PS4_Sup, BP4	{"Latino": null, "American": null, "European": 0.00009436, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": 0.00009667}	f
3685833	135	RYR1	c.12115A>T	Variant of uncertain significance	Uncertain function	\N	n/a	3685832	{35849058}	\N	\N	PS4_Sup	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685855	135	RYR1	c.12533G>T	Variant of uncertain significance	Uncertain function	\N	n/a	3685854	{35849058}	\N	\N	PS4_Mod, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685863	135	RYR1	c.12700G>T	Likely Pathogenic	Malignant Hyperthermia associated	\N	n/a	3685862	{35849058}	\N	\N	PS1_Mod, PS4_Mod, PP1, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685885	135	RYR1	c.13918A>G	Variant of uncertain significance	Uncertain function	\N	n/a	3685884	{33767344}	\N	\N	PS4_Sup, PM1_Sup, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685891	135	RYR1	c.13994_13995delTCinsCT	Variant of uncertain significance	Uncertain function	\N	n/a	3685890	{35849058}	\N	\N	PS2_PM6_Sup, PM1_Sup	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685915	135	RYR1	c.14422_14423delinsAA	Variant of uncertain significance	Uncertain function	\N	n/a	3685914	{35849058}	\N	\N	PM1_Sup	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
779237	323	RYR1	c.14497C>T	Likely Pathogenic	Malignant Hyperthermia associated	\N	n/a	779236	{33767344}	\N	\N	PS3_Mod, PS4_Mod, PM1_Sup, PP1_Mod, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
779725	282	CYP2D6	*29x2	\N	Normal function	\N	1.0	777990	{11470994,11823760}	Limited	\N	CYP2D6*29x2 is assigned normal function based on limited evidence. CYP2D6*29 is assigned decreased function based on subjects demonstrating decreased enzyme activity with various substrates (11470994, 11823760). Therefore, consensus among experts was normal function with an activity value of 1 based on limited evidence as it was determined the phenotypes containing a duplication of this allele would demonstrate greater enzyme activity than that of the nonduplicated allele and be clinically similar to phenotypes comprising normal function alleles.	{"Latino": 0.00018922375, "American": 0.0, "European": 0.0, "Oceanian": null, "East Asian": 0.0, "Near Eastern": null, "Central/South Asian": 0.0, "Sub-Saharan African": 0.003, "African American/Afro-Caribbean": 0.0010999363}	f
778143	339	CYP2D6	*112	\N	Uncertain function	\N	n/a	778142	{31368850}	Inadequate	\N	CYP2D6*112 is assigned uncertain function. CYP2D6*112 is defined by a SNP which in silico studies predict to be a benign amino acid change (31368850). Consensus was not achieved among experts as data were sparse. Therefore, uncertain function was assigned.	{"Latino": null, "American": 0.0, "European": 0.0, "Oceanian": null, "East Asian": 0.0, "Near Eastern": null, "Central/South Asian": 0.002, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.0}	f
2899149	133	CYP2B6	*42	Decreased function	Decreased function	\N	\N	2899148	{14551287,18171905,24260284,38596098}	Limited	\N	CYP2B6*42 (c.516G>T, p.Q172H/splice defect; c.785A>G, p.K262R; c.1328G>A, p.R443H) – Decreased function: CYP2B6*42 is assigned decreased function. CYP2B6*42 contains c.516G>T which causes aberrant splicing (see CYP2B6*6 for more information). As is the same for *6, the mechanism for decreased activity is aberrant splicing caused by c.516G>T, which leads to reduced amounts of protein and thus, activity (14551287, 18171905, 24260284). As a result, alleles having c.516G>T are considered decreased function, regardless of the functional status of additional other variants unless these cause no function (e.g., CYP2B6*13 and CYP2B6*38). A single in vitro study reported decreased function for p.R443H using buproprion and efavirez as probes (38596098). Therefore, the consensus among experts was decreased function based on the presence of c.516G>T and limited evidence.	{"Latino": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
777553	344	CYP2C19	*11	\N	Normal function	\N	\N	777552	{12464799,21325430,25001882,21692664}	Limited	\N	CYP2C19*11 is assigned normal function based on limited evidence. Three in vitro studies using different cell systems found CYP2C19*11 demonstrated similar enzyme activity compared to wildtype with mephenytoin, omeprazole, clopidogrel and other substrates (12464799, 21325430, 25001882, 21692664). Therefore, consensus among experts was normal function based on limited evidence as it was determined the phenotypes containing this allele would be clinically similar to phenotypes comprising normal function alleles.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": 0.0, "Near Eastern": 0.0, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
777977	340	CYP2D6	*22	\N	Uncertain function	\N	n/a	777976	{24647041,30366777}	Inadequate	\N	CYP2D6*22 is assigned uncertain function due to inadequate evidence. In vitro studies found CYP2D6*22 demonstrated enzyme activity ranging from increased to decreased activity compared to wildtype with various substrates (24647041, 30366777). Therefore, consensus among experts was uncertain function.	{"Latino": null, "American": 0.0, "European": 0.003, "Oceanian": null, "East Asian": 0.0, "Near Eastern": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.0}	f
778153	339	CYP2D6	*117	\N	Unknown function	\N	n/a	778152	{}	No Evidence	\N	CYP2D6*117 is assigned unknown function due to no literature describing function of this allele. Therefore, consensus among experts was unknown function due to no available evidence.	{"Latino": null, "American": 0.0, "European": 0.004, "Oceanian": null, "East Asian": 0.0, "Near Eastern": null, "Central/South Asian": 0.0, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.0}	f
778797	296	G6PD	Malaga	III/Deficient	III/Deficient	\N	\N	778796	{22293322,8956035,22963789}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": 0.00028541868, "European": 0.00001806179, "East Asian": 0.0, "Central/South Asian": 0.0, "African American/Afro-Caribbean": 0.0011595425}	f
3827901	117	MT-RNR1	m.961T>del+Cn	\N	uncertain risk of aminoglycoside-induced hearing loss	\N	\N	3827900	{10326749,12037390,7550368,20171168}	\N	\N	MT-RNR1 961>del+Cn is assigned an uncertain risk of aminoglycoside-induced hearing loss based on inadequate evidence. Screening of individuals with aminoglycoside-hearing loss identified this variant in three studies and one case report (10326749, 12037390, 7550368); however, one study found this variant in patients without aminoglycoside-induced hearing loss (20171168). Therefore, consensus among experts is that there is uncertain risk of aminoglycoside-induced hearing loss associated with this variant.	{"European": 0.002636598, "East Asian": 0.04951802, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": 0.06856881}	f
3827907	117	MT-RNR1	m.1189T>C	\N	uncertain risk of aminoglycoside-induced hearing loss	\N	\N	3827906	{22030963}	Inadequate evidence	\N	MT-RNR1 1189T>Cis assigned an uncertain risk of aminoglycoside-induced hearing loss based on inadequate evidence. Screening of individuals with aminoglycoside-hearing loss identified this variant in one study (22030963). Therefore, consensus among experts was uncertain risk of aminoglycoside-induced hearing loss due to insufficient evidence.	{"European": 0.056569297, "East Asian": 0.0006752, "Near Eastern": 0.22850867, "Central/South Asian": 0.006698, "Sub-Saharan African": null}	f
779245	323	RYR1	c.14693T>C	Variant of uncertain significance	Uncertain function	\N	n/a	779244	{}	\N	\N	PM1_Sup, PP3_Mod, BS3_Sup	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685965	135	RYR1	c.14813T>C	Variant of uncertain significance	Uncertain function	\N	n/a	3685964	{35849058}	\N	\N	PS3_Mod, PS4_Sup, PM1_Sup, PP3_Mod, BS2_Mod, BS3_Sup	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685969	135	RYR1	c.14817C>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685968	{35849058}	\N	\N	PS4_Sup, PM1_Sup	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
1777304	256	CYP2D6	*1x≥3	\N	Increased function	\N	≥3.0	777936	{7616439,9012401}	Limited	\N	CYP2D6*1x≥3 is assigned increased function based on limited evidence. Subjects with CYP2D6 gene duplications demonstrated increased enzyme activity with the greatest debrisoquine metabolism among 270 subjects based on urine metabolites (7616439). Additionally, debrisoquine metabolism correlated with the number of functional CYP2D6 genes (7616439, 9012401). Therefore, consensus among experts was increased function with an activity value of ≥3 based on limited evidence as it was determined the phenotypes containing this allele would be clinically distinct from phenotypes comprising normal function alleles.	{"Latino": 0.00050, "American": 0.001, "European": 0.0006873065, "Oceanian": null, "East Asian": 0.0, "Near Eastern": null, "Central/South Asian": 0.0, "Sub-Saharan African": 0.002, "African American/Afro-Caribbean": 0.0}	f
779025	296	G6PD	Neapolis	III/Deficient	III/Deficient	\N	\N	779024	{22293322,9233561}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": 0.0, "European": 0.0, "East Asian": 0.0, "Central/South Asian": 0.0, "African American/Afro-Caribbean": 0.0}	f
3685425	135	RYR1	c.1553T>C	Variant of uncertain significance	Uncertain function	\N	n/a	3685424	{35849058}	\N	\N	PM1	{"Latino": null, "American": null, "European": 0.00002941, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685811	135	RYR1	c.11708G>A	Likely Pathogenic	Malignant Hyperthermia associated	\N	n/a	3685810	{35849058}	\N	\N	PS4, PP3_Mod	{"Latino": null, "American": null, "European": 0.0000294, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
779093	115	NUDT15	*15	\N	\N	\N	\N	779092	\N	\N	\N	\N	\N	f
3685979	135	RYR1	c.14968A>G	Variant of uncertain significance	Uncertain function	\N	n/a	3685978	{35849058}	\N	\N	PS4_Sup, PM1_Sup	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
779328	322	SLCO1B1	*26	\N	Uncertain function	\N	\N	779327	{22147369,33658230}	Inadequate	\N	SLCO1B1*26 is assigned uncertain function based on limited in vitro evidence and clinical data. One clinical study showed no statistical difference in methotrexate clearance (22147369) and one in vitro study found normal protein expression (33658230). Therefore, consensus among experts was uncertain function due to inadequate evidence.	{"American": null, "European": 0.00020, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": 0.00030, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778147	340	CYP2D6	*114	\N	No function	\N	0.0	778146	{10064570,18784265,24647041}	Limited	\N	CYP2D6*114 is assigned no function based on limited evidence. CYP2D6*114 has been described in a subject with CYP2D6*5/*114 genotype demonstrating poor debrisoquine metabolism (10064570). Multiple in vitro studies found CYP2D6*114 had nondetectable enzyme activity with various substrates (18784265, 24647041). Therefore, consensus among experts was no function with an activity value of 0 based on limited evidence.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": 0.0007862866, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778725	296	G6PD	Lagosanto	III/Deficient	III/Deficient	\N	\N	778724	{22293322,8370579}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": 0.0, "European": 0.000010254307, "East Asian": 0.0, "Central/South Asian": 0.0, "African American/Afro-Caribbean": 0.0}	f
778829	296	G6PD	Nanning	III/Deficient	III/Deficient	\N	\N	778828	{22293322,17018380}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": 0.0, "European": 0.0, "East Asian": 0.00033690452, "Central/South Asian": 0.0, "African American/Afro-Caribbean": 0.0}	f
3685461	135	RYR1	c.2654G>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685460	{35849058}	\N	\N	None	{"Latino": 0.00006545, "American": null, "European": 0.0002205, "East Asian": 0.0003857, "Near Eastern": null, "Central/South Asian": 0.0004146, "Sub-Saharan African": 0.00007237}	f
3685485	135	RYR1	c.3656A>C	Variant of uncertain significance	Uncertain function	\N	n/a	3685484	{35849058}	\N	\N	PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685805	135	RYR1	c.11314C>T	Variant of uncertain significance	Uncertain function	\N	n/a	3685804	{33767344}	\N	\N	PS4_Sup, PM5_Sup, PP3_Mod	{"Latino": 0.00006547, "American": null, "European": 0.0000294, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
778853	296	G6PD	Haikou	II/Deficient	II/Deficient	\N	\N	778852	{22293322,11295127}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
3685393	135	RYR1	c.1024G>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685392	{35849058}	\N	\N	PS4_Sup, PM1, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685413	135	RYR1	c.1411C>T	Variant of uncertain significance	Uncertain function	\N	n/a	3685412	{35849058}	\N	\N	PM1	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685497	135	RYR1	c.4747C>T	Variant of uncertain significance	Uncertain function	\N	n/a	3685496	{35849058}	\N	\N	None	{"Latino": null, "American": null, "European": 0.00012714975, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": 0.00002414}	f
779284	322	SLCO1B1	*4	\N	Uncertain function	\N	\N	779283	{11477075,12490595,33658230}	Inadequate	\N	SLCO1B1*4 is assigned uncertain function based on in vitro studies demonstrating unaltered uptake of estrone sulfate, estradiol 17beta-d-glucuronide and rifampin (11477075, 12490595) and normal protein expression (33658230), but no clinical data. Therefore, consensus among experts was uncertain function due to inadequate evidence.	{"American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
779304	323	SLCO1B1	*14	Increased function	Increased function	\N	\N	779303	{11477075,22147369,23311897,24122874,18781850,24420746,31777781,20139798,32961594}	Strong	\N	SLCO1B1*14 is assigned increased function based on strong evidence in heterozygous and homozygous patients. The lipid-lowering response to fluvastatin is associated with the *14 allele, with greater response in the *14/*14 patients (18781850). The clearance of high-dose methotrexate is significantly faster in patients with two *14 alleles (22147369), and response to low-dose methotrexate is reduced in patients with arthritis (31777781). Exposure to atorvastatin is decreased in heterozygous and homozygous subjects (23311897). The plasma levels of highly sensitive OATP1B1 endogenous substrate GCDCA-3G are significantly lower in *14 carriers than in individuals with the SLCO1B1*1/*1 diplotype (32961594). The *14 allele is associated with increased expression of the transporter in the liver (23311897, 24122874). In vitro studies that normalize the drug uptake to the protein concentration find no increased uptake of rifampin, estrone sulfate, or estradiol 17beta-glucuronide (11477075) and one found decreased uptake of estrone sulfate and ceravistatin (23652407). Therefore, consensus among experts was increased function.	{"American": null, "European": 0.135571, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": null}	f
779316	322	SLCO1B1	*20	Increased function	Increased function	\N	\N	779315	{15226675,22147369,23311897,32961594}	Limited	\N	SLCO1B1*20 is assigned increased function based on limited in vitro evidence and limited clinical data. Small clinical studies of pravastatin and atorvastatin showed similar pharmacokinetic parameters to subjects with wildtype alleles (15226675, 23311897). One clinical study found significantly increased methotrexate clearance (22147369). The plasma levels of highly sensitive OATP1B1 endogenous substrate GCDCA-3G are significantly lower in *14 carriers than in individuals with the SLCO1B1*1/*1 diplotype (32961594). Therefore, consensus among experts was increased function due to inadequate evidence.	{"American": null, "European": 0.037392758, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
779330	322	SLCO1B1	*27	\N	Uncertain function	\N	\N	779329	{22147369,33658230}	Inadequate	\N	SLCO1B1*27 is assigned uncertain function based on limited in vitro evidence and clinical data. One clinical study showed no statistical difference in methotrexate clearance (22147369) and one in vitro study found normal protein expression (33658230). Therefore, consensus among experts was uncertain function due to inadequate evidence.	{"American": null, "European": null, "Oceanian": null, "East Asian": 0.0, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
779334	322	SLCO1B1	*29	\N	Uncertain function	\N	\N	779333	{22147369,33658230}	Inadequate	\N	SLCO1B1*29 is assigned uncertain function based on limited in vitro evidence and limited clinical data. One clinical study showed no statistical difference in methotrexate clearance (22147369) and one in vitro study found normal protein expression (33658230). Therefore, consensus among experts was uncertain function due to inadequate evidence.	{"American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778209	246	CYP2D6	*145	\N	Uncertain function	\N	n/a	778208	{24647041,30366777}	Inadequate	\N	CYP2D6*145 is assigned uncertain function due to inadequate evidence. CYP2D6*145 is defined by the insertion of three amino acids which also define CYP2D6*30; *145 lacks two others also present in *30. In vitro studies demonstrated decreased enzyme activity for *30 compared to *1 with tamoxifen, bufuralol, dextromethorphan, and primaquine substrates (24647041, 30366777). Therefore, consensus among experts was uncertain function.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
2955640	175	CYP2D6	*146x2	\N	Uncertain function	\N	n/a	1103377	{}	Inadequate	\N	CYP2D6*146x2 is assigned uncertain function. CYP2D6*146 is defined by three SNPs all of which have been found in other star alleles; none of these SNPs have been implicated to cause no function; two are the defining SNPs of the normal function *2 allele and one is the defining SNP of uncertain function *43 allele. Therefore, consensus among experts for *146 and *146x2 was uncertain function.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": 0.00052, "African American/Afro-Caribbean": null}	f
3685421	135	RYR1	c.1460T>C	Variant of uncertain significance	Uncertain function	\N	n/a	3685420	{35849058}	\N	\N	PS4_Sup, PM1, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
779177	323	RYR1	c.1597C>T	Pathogenic	Malignant Hyperthermia associated	\N	n/a	779176	{33767344}	\N	\N	PS3_Mod, PS4_Sup, PM1, PP1_St, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": 0.00002414}	f
3685751	135	RYR1	c.9635A>G	Variant of uncertain significance	Uncertain function	\N	n/a	3685750	{35849058}	\N	\N	None	{"Latino": 0.00006544, "American": null, "European": 0.00059750484, "East Asian": null, "Near Eastern": 0.0002884, "Central/South Asian": null, "Sub-Saharan African": 0.00009651}	f
3685759	135	RYR1	c.9758T>C	Variant of uncertain significance	Uncertain function	\N	n/a	3685758	{33767344}	\N	\N	None	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": 0.0001935}	f
3685765	135	RYR1	c.9850T>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685764	{35849058}	\N	\N	PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685777	135	RYR1	c.10229C>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685776	{35849058}	\N	\N	PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685785	135	RYR1	c.10616G>A	Likely Benign	Normal function	\N	n/a	3685784	{35849058}	\N	\N	PP3_Mod, BS1, BS2	{"Latino": 0.0002625, "American": null, "European": 0.0027869444, "East Asian": null, "Near Eastern": null, "Central/South Asian": 0.000416, "Sub-Saharan African": 0.0005563}	f
3685789	135	RYR1	c.10750G>C	Variant of uncertain significance	Uncertain function	\N	n/a	3685788	{35849058}	\N	\N	None	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685821	135	RYR1	c.11947C>T	Variant of uncertain significance	Uncertain function	\N	n/a	3685820	{33767344}	\N	\N	PS2_PM6_Mod, PS4_Sup, PP3_Mod, BS3_Sup	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685823	135	RYR1	c.11953T>C	Variant of uncertain significance	Uncertain function	\N	n/a	3685822	{35849058}	\N	\N	PS4_Mod, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
779338	323	SLCO1B1	*31	Decreased function	No function	\N	\N	779337	{22147369,39511784}	Moderate	\N	SLCO1B1*31 is assigned no function based on moderate evidence. SLCO1B1*31 is defined by c.388A>G (p.N130D, defining *37) and c.1463G>C (p.G488A, defining *9). SLCO1B1*37 is assigned normal function based on strong evidence as c.388A>G was not associated with altered clearance of SLCO1B1-transported drugs. SLCO1B1*9 is assigned no function based on moderate in vitro and clinical evidence. An individual genotyped SLCO1B1*1/*31 exhibited markedly decreased high-dose methotrexate clearance compared to the reference allele, and clearance was decreased compared to a SLCO1B1*5/*5 patient (22147369). An individual genotyped SLCO1B1*31/*41 exhibited an elevated plasma concentration of coproporphyrin I, at a level comparable to SLCO1B1*15/*15 patients, and this individual experienced statin-induced rhabdomyolysis (39511784). In vitro uptake of methotrexate by protein encoded by SLCO1B1*31 was significantly decreased compared to the reference; transport activity was similar to empty vector controls (22147369). Ten out of ten variant effect predictors (VEPs) tested by CPIC staff predict that c.388A>G is neutral for protein function. Nine out of ten VEPs predict that c.1463G>C impairs protein function.	{"American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
1002686	316	SLCO1B1	*37	\N	Normal function	\N	\N	1002685	{32961594,32961019,11477075}	Strong	\N	SLCO1B1*37 is assigned normal function based on strong evidence in heterozygous and homozygous individuals. The plasma levels of highly sensitive OATP1B1 endogenous substrates GCDCA-3G, GDCA-3G and CPI are slightly and non-significantly lower in SLCO1B1*37 homozygotes (32961594, 32961019). In vitro studies have mostly demonstrated unaltered activity compared to SLCO1B1*1 (11477075).	{"American": 0.39, "European": 0.25273752, "Oceanian": 0.66, "East Asian": 0.6147381, "Near Eastern": 0.31, "Central/South Asian": 0.46023798, "Sub-Saharan African": 0.80076206, "African American/Afro-Caribbean": 0.76}	f
778931	296	G6PD	Lynwood	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778930	{22293322,1945893}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
778869	296	G6PD	Montalbano	III/Deficient	III/Deficient	\N	\N	778868	{22293322,11146567,2321910}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": 0.0, "European": 0.0, "East Asian": 0.0, "Central/South Asian": 0.0, "African American/Afro-Caribbean": 0.000076028286}	f
778927	296	G6PD	Olomouc	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778926	{22293322,7655862}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
3685365	135	RYR1	c.533A>C	Variant of uncertain significance	Uncertain function	\N	n/a	3685364	{35849058}	\N	\N	PS4_Sup, PM1, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
777801	326	CYP2C9	*67	Uncertain function	Uncertain function	\N	n/a	777800	{33536773}	Inadequate evidence	\N	CYP2C9*67 is assigned uncertain funciton due to inadequate evidence. The nonsynonymous variants present in CYP2C9*67 are predicted to be deleterious in both SIFT and Polyphen predictions. There are no in vitro or clinical studies reported. Consensus was not achieved among experts and therefore uncertain function was assigned.	{"Latino": 0.00010, "American": null, "European": 0.0, "Oceanian": null, "East Asian": null, "Near Eastern": 0.0, "Central/South Asian": 0.00020, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778695	296	G6PD	Palestrina	III/Deficient	III/Deficient	\N	\N	778694	{22293322}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
3827881	117	MT-RNR1	m.807A>C	\N	uncertain risk of aminoglycoside-induced hearing loss	\N	\N	3827880	{18830133}	Inadequate evidence	\N	MT-RNR1 807A>C is assigned an uncertain risk of aminoglycoside-induced hearing loss based on inadequate evidence. Screening of individuals with aminoglycoside-hearing loss identified this variant in one study (18830133). Therefore, consensus among experts was uncertain risk of aminoglycoside-induced hearing loss due to insufficient evidence.	{"European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685335	135	RYR1	c.418G>A	Likely Benign	Normal function	\N	n/a	3685334	{35849058}	\N	\N	PM1, BS2_Mod, BP4	{"Latino": null, "American": null, "European": 0.0002058, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": 0.00002414}	f
3685351	135	RYR1	c.493G>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685350	{35849058}	\N	\N	PS4_Sup, PM1, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
778185	339	CYP2D6	*133	\N	Uncertain function	\N	n/a	778184	{32759992}	Inadequate	\N	CYP2D6*133 is assigned uncertain function due to inadequate literature describing function of this allele. One in vitro study demonstrated substabtially decreased intrinsic clearance CLint (Vmax/Km) of 2.5% and 4.5% compared to *1 for tamoxifen N-desmethylation and dextromethorphan O-demethylation, respectively. Therefore, consensus among experts was uncertain function due to inadequate evidence.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778360	331	DPYD	c.775A>G	Normal function	Normal function	\N	1.0	778359	{25410891}	Limited	\N	5-fluorouracil (in vitro)	{"Latino": 0.007314514, "European": 0.015303651, "East Asian": 0.0, "Central/South Asian": 0.0068804934, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.0030573248}	f
779033	296	G6PD	Campinas	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	779032	{22293322,8477268}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
3685367	135	RYR1	c.625G>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685366	{35849058}	\N	\N	PM1, BP2	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685381	135	RYR1	c.946C>T	Variant of uncertain significance	Uncertain function	\N	n/a	3685380	{35849058}	\N	\N	PM1	{"Latino": null, "American": null, "European": 0.0000147, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685383	135	RYR1	c.947G>T	Variant of uncertain significance	Uncertain function	\N	n/a	3685382	{35849058}	\N	\N	PM1, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": 0.0003861, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
779163	323	RYR1	c.982C>T	Likely Pathogenic	Malignant Hyperthermia associated	\N	n/a	779162	{33767344}	\N	\N	PS3_Mod, PS4_Sup, PM1, PP1	{"Latino": null, "American": null, "European": 0.0001883, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685841	135	RYR1	c.12310G>C	Likely Benign	Normal function	\N	n/a	3685840	{35849058}	\N	\N	BS2_Mod, BP4	{"Latino": null, "American": null, "European": 0.0000147, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685395	135	RYR1	c.1100G>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685394	{35849058}	\N	\N	PS4_Mod, PM1	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685539	135	RYR1	c.6387C>G	Likely Pathogenic	Malignant Hyperthermia associated	\N	n/a	3685538	{35849058}	\N	\N	PS4_Mod, PM1, PP1_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685835	135	RYR1	c.12121C>T	Variant of uncertain significance	Uncertain function	\N	n/a	3685834	{35849058}	\N	\N	BP4	{"Latino": null, "American": null, "European": 0.0000147, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
778366	331	DPYD	c.934C>T	Normal function	Normal function	\N	1.0	778365	{24648345}	Limited	\N	5-fluorouracil (in vitro)	{"Latino": 0.0, "European": 0.000013648715, "East Asian": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778729	296	G6PD	Urayasu	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778728	{22293322,7849299}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
779171	323	RYR1	c.1209C>G	Variant of uncertain significance	Uncertain function	\N	n/a	779170	{}	\N	\N	PS3_Mod, PM1, BS2_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
777569	344	CYP2C19	*19	\N	Decreased function	\N	\N	777568	{17455109,18312490,21325430,25001882,21692664}	Limited	\N	CYP2C19*19 is assigned decreased function based on limited evidence. In vitro studies found CYP2C19*19 had decreased intrinsic clearance compared to wildtype with mephenytoin, omeprazole, and clopidogrel substrates (17455109, 21325430, 25001882). Although two in vitro studies found CYP2C19*19 demonstrated similar intrinsic clearance compared to wildtype with omeprazole and mephenytoin, the experts did not find these results convincing as CYP2C19*19 also demonstrated higher Km values compared to wildtype in these studies, suggesting CYP2C19*19 has decreased substrate affinity (18312490, 21325430). Additionally, decreased intrinsic clearance compared to wildtype with these two substrates was previously reported as mentioned above. Another study found CYP2C19*19 exhibited significantly reduced catalytic activities compared with CYP2C19*1 across multiple substrates (21692664).Therefore, consensus among experts was decreased function based on limited evidence as it was determined the phenotypes containing this allele would be clinically distinct from phenotypes comprising normal function alleles.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": 0.00019673406, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
3685533	135	RYR1	c.6304G>C	Variant of uncertain significance	Uncertain function	\N	n/a	3685532	{35849058}	\N	\N	PM1	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
777951	340	CYP2D6	*8	\N	No function	\N	0.0	777950	{8530011}	Limited	\N	CYP2D6*8 is assigned no function based on limited evidence. CYP2D6*8 was first described in a subject demonstrating decreased debrisoquine and sparteine metabolism (8530011). CYP2D6*8 is defined by an amino substitution resulting in a premature stop codon yielding a truncated and nonfunctional protein. Therefore, consensus among experts was no function with an activity value of 0 based on limited evidence as it was determined the phenotypes containing this allele would be clinically distinct from phenotypes comprising normal and decreased function alleles.	{"Latino": 0.0, "American": 0.0010120482, "European": 0.00022450546, "Oceanian": 0.0, "East Asian": 0.0, "Near Eastern": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.0}	f
3685513	135	RYR1	c.5186T>G	Variant of uncertain significance	Uncertain function	\N	n/a	3685512	{35849058}	\N	\N	PS4_Sup	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3827903	117	MT-RNR1	m.988G>A	\N	uncertain risk of aminoglycoside-induced hearing loss	\N	\N	3827902	{18830133}	Inadequate evidence	\N	MT-RNR 988G>A is assigned an uncertain risk of aminoglycoside-induced hearing loss based on inadequate evidence. Screening of individuals with aminoglycoside-hearing loss identified this variant in one study (18830133). Therefore, consensus among experts was uncertain risk of aminoglycoside-induced hearing loss due to insufficient evidence.	{"European": 0.0010754358, "East Asian": 0.0, "Near Eastern": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": null}	f
3685515	135	RYR1	c.5317C>T	Benign	Normal function	\N	n/a	3685514	{33767344}	\N	\N	BA1	{"Latino": null, "American": null, "European": null, "East Asian": 0.01348, "Near Eastern": null, "Central/South Asian": 0.0002069, "Sub-Saharan African": null}	f
3685597	135	RYR1	c.7032G>C	Variant of uncertain significance	Uncertain function	\N	n/a	3685596	{35849058}	\N	\N	PM1	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
779203	323	RYR1	c.7063C>T	Pathogenic	Malignant Hyperthermia associated	\N	n/a	779202	{33767344}	\N	\N	PS3_Mod, PS4, PM1, PP1_St, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": 0.0002075, "Sub-Saharan African": null}	f
3685741	135	RYR1	c.9152G>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685740	{35849058}	\N	\N	None	{"Latino": null, "American": null, "European": 0.00001471, "East Asian": null, "Near Eastern": 0.004323, "Central/South Asian": null, "Sub-Saharan African": 0.00002416}	f
3685845	135	RYR1	c.12383C>T	Variant of uncertain significance	Uncertain function	\N	n/a	3685844	{35849058}	\N	\N	PS4_Sup, BP4	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685857	135	RYR1	c.12553G>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685856	{35849058}	\N	\N	BP4	{"Latino": 0.0008509, "American": null, "European": 0.0005145, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": 0.0001448}	f
3685889	135	RYR1	c.13990T>C	Variant of uncertain significance	Uncertain function	\N	n/a	3685888	{35849058}	\N	\N	PS4_Sup, PM1_Sup, PP3_Mod	{"Latino": null, "American": null, "European": 0.00001481, "East Asian": null, "Near Eastern": 0.0005784, "Central/South Asian": null, "Sub-Saharan African": null}	f
778897	296	G6PD	Fushan	II/Deficient	II/Deficient	\N	\N	778896	{22293322,7803800}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
778681	296	G6PD	Gidra	Uncertain	Uncertain function	\N	\N	778680	{22293322,9410474}	Inadequate	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
3685505	135	RYR1	c.5033A>G	Variant of uncertain significance	Uncertain function	\N	n/a	3685504	{35849058}	\N	\N	BP4	{"Latino": 0.0000654, "American": null, "European": 0.0000147, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
777495	344	CYP2B6	*38	No function	No function	\N	\N	777494	{23640958}	Limited	\N	CYP2B6*38 (c.186T>A, p.Y62X; c.516G>T, p.Q172H/splice defect; c.785A>G, p.K262R) – No function: CYB2B6*38 is assigned no function. CYP2B6*38 contains the variants which define CYP2B6*6 in addition to a third variant which causes a premature stop codon. CYP2B6*38 was identified in a patient taking efavirenz who developed neurologic symptoms and was found to have an efavirenz plasma concentration 40-fold above normal limit. Efavirenz was discontinued and efavirenz plasma concentrations returned to normal after 10 weeks in addition to resolution of neurologic symptoms (23640958). Therefore, consensus among experts was no function based on limited evidence.	{"Latino": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
779189	323	RYR1	c.6488G>A	Pathogenic	Malignant Hyperthermia associated	\N	n/a	779188	{33767344}	\N	\N	PS3_Mod, PS4, PM1, PP1_St, PP3_Mod, BS2	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
1777307	256	CYP2D6	*2x≥3	\N	Increased function	\N	≥3.0	777938	{7616439,7903454,8764380}	Limited	\N	CYP2D6*2x≥3 is assigned increased function based on limited evidence. CYP2D6*2x≥3 was described in a family demonstrating increased enzyme activity based on urine metabolites with a debrisoquine substrate (7903454). Subjects with CYP2D6 gene duplications demonstrated increased enzyme activity with the greatest debrisoquine metabolism among all subjects (7616439, 8764380). Therefore, consensus among experts was increased function with an activity value of ≥3 based on limited evidence as it was determined the phenotypes containing this allele would be clinically distinct from phenotypes comprising normal function alleles.	{"Latino": 0.00050, "American": 0.0, "European": 0.001, "Oceanian": null, "East Asian": 0.001, "Near Eastern": null, "Central/South Asian": 0.0, "Sub-Saharan African": 0.003, "African American/Afro-Caribbean": 0.0}	f
778442	325	DPYD	c.1990G>T	Normal function	Normal function	\N	1.0	778441	{24648345}	Limited	\N	5-fluorouracil (in vitro)	{"Latino": 0.0, "European": 0.0, "East Asian": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778839	296	G6PD	Roubaix	II/Deficient	II/Deficient	\N	\N	778838	{22293322,22139979}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
778991	296	G6PD	Santiago de Cuba, Morioka	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778990	{22293322,9192788,3393536}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
3827877	117	MT-RNR1	m.747A>G	\N	uncertain risk of aminoglycoside-induced hearing loss	\N	\N	3827876	{21205314}	Inadequate evidence	\N	MT-RNR1 747A>G is assigned an uncertain risk of aminoglycoside-induced hearing loss based on inadequate evidence. Screening of individuals with aminoglycoside-hearing loss identified this variant in one study (21205314). Therefore, consensus among experts was uncertain risk of aminoglycoside-induced hearing loss due to insufficient evidence.	{"European": 0.0, "East Asian": 0.0, "Near Eastern": 0.0, "Central/South Asian": 0.00134, "Sub-Saharan African": null}	f
3685551	135	RYR1	c.6488G>T	Likely Pathogenic	Malignant Hyperthermia associated	\N	n/a	3685550	{35849058}	\N	\N	PS4_Sup, PM1_Sup, PM5, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685567	135	RYR1	c.6628G>T	Likely Pathogenic	Malignant Hyperthermia associated	\N	n/a	3685566	{35849058}	\N	\N	PS4_Mod, PM1, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685771	135	RYR1	c.10043G>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685770	{35849058}	\N	\N	PS4_Sup	{"Latino": null, "American": null, "European": 0.0000147, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
779195	323	RYR1	c.6617C>T	Pathogenic	Malignant Hyperthermia associated	\N	n/a	779194	{33767344}	\N	\N	PS3_Mod, PS4, PM1_Sup, PM5, PP1_St, PP3_Mod, BS2	{"Latino": null, "American": null, "European": 0.00006357385, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": 0.00002413}	f
779288	323	SLCO1B1	*6	\N	Uncertain function	\N	\N	779287	{11477075,12490595}	Inadequate	\N	SLCO1B1*6 is assigned uncertain function based on in vitro studies demonstrating reduced uptake of estrone sulfate, estradiol 17beta-d-glucuronide and rifampin (11477075, 12490595), but no clinical data. Therefore, consensus among experts was uncertain function due to inadequate evidence.	{"American": null, "European": 0.0, "Oceanian": null, "East Asian": 0.0, "Near Eastern": null, "Central/South Asian": 0.0, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
1002702	316	SLCO1B1	*45	\N	No function	\N	\N	1002701	{38674010,32082363,36964102,39071607,25546334,40199401,37674011}	Moderate	\N	SLCO1B1*45 is assigned no function based on moderate evidence. SLCO1B1*45 is defined by c.1738C>T (p.R580X). This variant generates a premature stop codon resulting in the expression of a truncated protein. SLCO1B1*45 was significantly associated with increased bilirubin levels and an individual carrying SLCO1B1*45 experienced statin-associated muscle symptoms (38674010). Additionally, SLCO1B1 loss-of-function has been implicated in the pathogenesis of Rotor syndrome and SLCO1B1*45 has been identified in a homozygous state in probands (32082363, 36964102, 39071607, 25546334). Cryo-EM structural studies of SLCO1B1 protein have consistently identified p.R580 as a critical amino acid involved in substrate recognition and binding (40199401, 37674011). The SLCO1B1 protein contains 12 transmembrane domains; a truncation at p.R580 eliminates the final two transmembrane domains which is highly disruptive rendering the protein non-functional, as the full transmembrane architecture is required for substrate transport. Four out of four VEPs capable of making predictions for nonsense variants predict that c.1738C>T impairs protein function.	{"American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
1002624	316	SLCO1B1	*1	\N	Normal function	\N	\N	1002623	{10601278,10644574,10358072,12811365,15116054,15226675,21245207,32961594}	Definitive	\N	SLCO1B1*1 is the reference allele, associated with normal OATP1B1 activity based on a large number of in vitro (10601278, 10644574, 10358072) and clinical data (12811365, 15116054, 15226675, 21245207, 32961594).	{"American": 0.37, "European": 0.4027496, "Oceanian": 0.33999997, "East Asian": 0.25522262, "Near Eastern": 0.49, "Central/South Asian": 0.46972018, "Sub-Saharan African": 0.17130345, "African American/Afro-Caribbean": 0.23000002}	t
779393	322	TPMT	*1	\N	Normal function	\N	\N	779392	{}	\N	\N	\N	{"Latino": 0.94345534, "European": 0.9534313, "East Asian": 0.979625, "Near Eastern": 0.96561086, "Central/South Asian": 0.9813701, "Sub-Saharan African": 0.9214915, "African American/Afro-Caribbean": 0.92341334}	t
2899157	133	CYP2B6	*46	\N	Uncertain function	\N	\N	2899156	{38596098}	Inadequate	\N	CYP2B6*46 (c.740A>C, p.H247P) – Uncertain function: CYP2B6*46 is assigned uncertain function due to inadequate evidence describing function. A single in vitro study reported decreased function for p.H247P using buproprion and efavirez as probes (38596098).	{"Latino": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
777779	344	CYP2C9	*56	Uncertain function	Uncertain function	\N	n/a	777778	{24077631,24118918,25142737,25144335,25476996,25832633,25884291,25951663,25924705,27163851,23844998}	Inadequate evidence	\N	CYP2C9*56 is assigned uncertain function due to inadequate evidence. In vitro studies found CYP2C9*56 demonstrated enzyme activity ranging from decreased to increased compared to wildtype with various substrates (24077631, 24118918, 25142737, 25144335, 25476996, 25832633, 25951663, 25884291, 25924705, 27163851, 23844998). Therefore, consensus among experts was uncertain function due to inadequate evidence.	{"Latino": 0.0, "American": null, "European": 0.0, "Oceanian": null, "East Asian": null, "Near Eastern": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778801	297	G6PD	Mediterranean, Dallas, Panama, Sassari, Cagliari, Birmingham	II/Deficient	II/Deficient	\N	\N	778800	{22293322,7959686,18226470,11146567,7440223,3393536}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": 0.0, "European": 0.0005865103, "East Asian": 0.0, "Central/South Asian": 0.017349826, "African American/Afro-Caribbean": 0.0002108926}	f
778685	296	G6PD	Orissa	III/Deficient	III/Deficient	\N	\N	778684	{22293322,8533762,20621077}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": 0.0, "European": 0.0, "East Asian": 0.0, "Central/South Asian": 0.0016250786, "African American/Afro-Caribbean": 0.0}	f
778919	296	G6PD	Tenri	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778918	{22293322}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
3685465	135	RYR1	c.2924G>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685464	{35849058}	\N	\N	PS4_Sup, BP4	{"Latino": null, "American": null, "European": 0.0000147, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685477	135	RYR1	c.3172G>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685476	{35849058}	\N	\N	PS4_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685501	135	RYR1	c.4775C>T	Variant of uncertain significance	Uncertain function	\N	n/a	3685500	{35849058}	\N	\N	PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": 0.00002414}	f
3685557	135	RYR1	c.6548G>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685556	{35849058}	\N	\N	PS4_Sup, PM1	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685901	135	RYR1	c.14186A>C	Variant of uncertain significance	Uncertain function	\N	n/a	3685900	{35849058}	\N	\N	PM1_Sup	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685903	135	RYR1	c.14197T>G	Variant of uncertain significance	Uncertain function	\N	n/a	3685902	{35849058}	\N	\N	PS4_Sup, PM1_Sup	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685905	135	RYR1	c.14201G>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685904	{35849058}	\N	\N	PS4_Sup, PM1_Sup, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685939	135	RYR1	c.14539G>C	Likely Pathogenic	Malignant Hyperthermia associated	\N	n/a	3685938	{35849058}	\N	\N	PS4_Sup, PM1_Sup, PP1_St	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
779282	323	SLCO1B1	*3	\N	Uncertain function	\N	\N	779281	{11477075,12490595}	Inadequate	\N	SLCO1B1*3 is assigned uncertain function based on in vitro studies demonstrating reduced uptake of estrone sulfate, estradiol 17beta-d-glucuronide and rifampin (11477075, 12490595), but no clinical data. Therefore, consensus among experts was uncertain function due to inadequate evidence.	{"American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
6235914	11	CYP4F2	*22	\N	\N	\N	\N	6235913	\N	\N	\N	\N	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
6235916	11	CYP4F2	*23	\N	\N	\N	\N	6235915	\N	\N	\N	\N	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778779	296	G6PD	Plymouth	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778778	{22293322,7577654}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
778857	296	G6PD	Seattle, Lodi, Modena, Ferrara II, Athens-like	III/Deficient	III/Deficient	\N	\N	778856	{22293322,7959686,11146567,7705842,5844610,7947250}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": 0.0002496968, "European": 0.0010703556, "East Asian": 0.0, "Central/South Asian": 0.00073390646, "African American/Afro-Caribbean": 0.000052246603}	f
778679	296	G6PD	Sunderland	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778678	{22293322,2005960}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
3685625	135	RYR1	c.7090T>G	Likely Pathogenic	Malignant Hyperthermia associated	\N	n/a	3685624	{35849058}	\N	\N	PS4_Mod, PM1, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685873	135	RYR1	c.13513G>C	Benign	Normal function	\N	n/a	3685872	{33767344}	\N	\N	BA1	{"Latino": 0.0019, "American": null, "European": 0.0050225807, "East Asian": null, "Near Eastern": 0.004899, "Central/South Asian": 0.00207, "Sub-Saharan African": 0.001231}	f
3685879	135	RYR1	c.13702C>G	Variant of uncertain significance	Uncertain function	\N	n/a	3685878	{33767344}	\N	\N	None	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685881	135	RYR1	c.13760C>T	Variant of uncertain significance	Uncertain function	\N	n/a	3685880	{35849058}	\N	\N	None	{"Latino": null, "American": null, "European": 0.00005879, "East Asian": null, "Near Eastern": 0.0002884, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685895	135	RYR1	c.14051T>C	Variant of uncertain significance	Uncertain function	\N	n/a	3685894	{35849058}	\N	\N	PS4_Sup, PM1_Sup, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685897	135	RYR1	c.14126C>T	Variant of uncertain significance	Uncertain function	\N	n/a	3685896	{33767344}	\N	\N	PM1_Sup, PP3_Mod, BS3_Sup	{"Latino": null, "American": null, "European": null, "East Asian": 0.0001928, "Near Eastern": 0.001442, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685899	135	RYR1	c.14168G>A	Likely Benign	Normal function	\N	n/a	3685898	{35849058}	\N	\N	PM1_Sup, BS2_Mod	{"Latino": 0.0001965, "American": null, "European": 0.00007349, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": 0.00004827}	f
777479	344	CYP2B6	*30	No function	No function	\N	\N	777478	{23164804,28181240}	Limited	\N	CYP2B6*30 (CYP2B7-CYP2B6 hybrid gene) – No function: CYP2B6*30 is assigned no function. This allele has a hybrid gene consisting of CYP2B6 (exons 1-4) and CYP2B7 (exons 5-9) harboring 15 amino acid changes compared to the protein encoded by the CYP2B6*1 reference. Among those is a premature stop codon (p.R378X) which is also found in CYP2B6*28 (23164804). This allele has been found in a duplication structure; it remains uncertain, however, whether the other gene in the duplication is a *1, *4 or *6 (or potentially other). Although CYP2B6*30 has no function, the function of this duplication allele depends on the nature of the other gene copy. One in vitro study found that primary human hepatocytes of subjects with a CYP2B6*30 had significantly lower mRNA and protein expression and enzyme activity compared to the *1 reference (28181240). The same study also showed that the AUC for 4-OH-cyclophosphamide was significantly lower for patients with *1/*30 compared to *1/*1 (28181240). In this study, the presence of a CYP2B6*30 was inferred by subjects having three gene copies and sequence analysis of the *30; however, the study did not provide any information regarding the nature of the second gene copy of the duplication. Therefore, consensus among experts was no function based on limited evidence.	{"Latino": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
777543	344	CYP2C19	*6	\N	No function	\N	\N	777542	{9732415,21325430,25001882}	Limited	\N	CYP2C19*6 is assigned no function based on limited evidence in a heterozygous subject and in vitro studies. CYP2C19*6 was first described in a subject demonstrating decreased mephenytoin metabolism based on urine metabolite concentrations. This correlated with an in vitro study which found CYP2C19*6 had nondetectable enzyme activity with mephenytoin and tolbutamide substrates (9732415). Two additional in vitro studies using different cell systems found CYP2C19*6 had nondetectable enzyme activity with mephenytoin, omeprazole, and clopidogrel substrates (21325430, 25001882). Therefore, consensus among experts was no function based on limited evidence as it was determined the phenotypes containing this allele would be clinically distinct from phenotypes comprising normal function and decreased function alleles.	{"Latino": 0.0, "American": null, "European": 0.00030023712, "Oceanian": null, "East Asian": 0.0005600443, "Near Eastern": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.0}	f
778045	340	CYP2D6	*56	\N	No function	\N	0.0	778044	{16679388,17392730}	Limited	\N	CYP2D6*56 is assigned no function based on limited evidence. A subject with CYP2D6 *4/*56 genotype demonstrated poor dextromethorphan metabolism based on urine metabolites on multiple occasions (17392730). CYP2D6*56 was identified in an hepatocyte demonstrating undetectable CYP2D6 protein expression and undetectable enzyme activity with dextromethorphan and bufuralol substrates (16679388). CYP2D6*56 is defined by a premature stop codon yielding a truncated and nonfunctional protein. Therefore, consensus among experts was no function with an activity value of 0 based on limited evidence.	{"Latino": null, "American": 0.0, "European": 0.0008093927, "Oceanian": null, "East Asian": 0.0, "Near Eastern": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": 0.002, "African American/Afro-Caribbean": 0.0015748427}	f
778767	296	G6PD	Belem	II/Deficient	II/Deficient	\N	\N	778766	{22293322,12367584}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
3685907	135	RYR1	c.14209C>T	Likely Pathogenic	Malignant Hyperthermia associated	\N	n/a	3685906	{35849058}	\N	\N	PS4_Mod, PM1_Sup, PM5_Sup, PP1, PP3_Mod	{"Latino": null, "American": null, "European": 0.00002941, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685909	135	RYR1	c.14210G>A	Pathogenic	Malignant Hyperthermia associated	\N	n/a	3685908	{35849058}	\N	\N	PS4, PM1_Sup, PP1_St, PP3_Mod, BS2_Mod, PS3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685925	135	RYR1	c.14471T>C	Variant of uncertain significance	Uncertain function	\N	n/a	3685924	{35849058}	\N	\N	PS4_Mod, PM1_Sup, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
779419	322	TPMT	*12	\N	Uncertain function	\N	\N	779418	{18708949,13679074,27564568,16220112}	\N	\N	\N	{"Latino": 0.00008733, "European": null, "East Asian": 0.0000531, "Near Eastern": null, "Central/South Asian": 0.0, "Sub-Saharan African": null, "African American/Afro-Caribbean": 0.0}	f
777589	344	CYP2C19	*32	\N	Uncertain function	\N	\N	777588	{26153442,30464555,29098786}	Inadequate	\N	CYP2C19*32 is assigned uncertain function due to inadequate evidence. In vitro studies found CYP2C19*32 demonstrated enzyme activity ranging from decreased to similar activity compared to wildtype with various substrates (26153442, 30464555, 29098786). Consensus was not achieved among experts and therefore uncertain function was assigned.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": 0.00017527216, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778350	331	DPYD	c.525G>A	Normal function	Normal function	\N	1.0	778349	{23588312}	Limited	\N	5-fluorouracil (ex vivo)	{"Latino": 0.00014510652, "European": 0.0, "East Asian": 0.000081102364, "Central/South Asian": 0.0, "Sub-Saharan African": 0.0019642857, "African American/Afro-Caribbean": 0.0}	f
778833	296	G6PD	Stonybrook	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778832	{22293322,1611091}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
3685331	135	RYR1	c.212C>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685330	{35849058}	\N	\N	PM1, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685341	135	RYR1	c.467G>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685340	{35849058}	\N	\N	PM1, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
779155	323	RYR1	c.487C>T	Pathogenic	Malignant Hyperthermia associated	\N	n/a	779154	{33767344}	\N	\N	PS3, PS4, PM1_Sup, PM5_Sup, PP1_St, PP3_Mod, BS2_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
779157	323	RYR1	c.488G>T	Pathogenic	Malignant Hyperthermia associated	\N	n/a	779156	{33767344}	\N	\N	PS3_Mod, PS4_Mod, PM1, PP3_Mod, PP1_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685355	135	RYR1	c.497A>G	Variant of uncertain significance	Uncertain function	\N	n/a	3685354	{35849058}	\N	\N	PM1, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
779342	322	SLCO1B1	*33	\N	Uncertain function	\N	\N	779341	{22147369,33658230}	Inadequate	\N	SLCO1B1*33 is assigned uncertain function based on limited in vitro evidence and clinical data. One clinical study showed no statistical difference in methotrexate clearance (22147369) and one in vitro study found decreased protein expression (33658230). Therefore, consensus among experts was uncertain function due to inadequate evidence.	{"American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
779439	322	TPMT	*22	\N	Uncertain function	\N	\N	779438	{18708949,16917910}	\N	\N	\N	{"Latino": null, "European": 0.0, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
777531	344	CYP2C19	*38	\N	Normal function	\N	\N	777530	{2009263,32602114}	Definitve	\N	CYP2C19*38 is assigned normal function based on definitive evidence. CYP2C19*38 was originally catalogued as CYP2C19*1.001 (i.e. CYP2C19*1A) (2009263). Due to the standardized nomenclature system this allele received its own star designation and is now catalogued as CYP2C19*38 (32602114). Therefore, because CYP2C19*38 does not contain any single nucleotide polymorphisms and the new star designation was a result of nomenclature standardization, consensus among experts was normal function.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
2899143	133	CYP2B6	*39	Decreased function	Decreased function	\N	\N	2899142	{14551287,18171905,24260284,38596098}	Limited	\N	CYP2B6*39 (c.418C>T, p.R140W; c.516G>T, p.Q172H/splice defect; c.785A>G, p.K262R) – Decreased function: CYP2B6*39 is assigned decreased function. CYP2B6*39 contains c.516G>T which causes aberrant splicing (see CYP2B6*6 for more information). As is the same for *6, the mechanism for decreased activity is aberrant splicing caused by c.516G>T, which leads to reduced amounts of protein and thus, activity (14551287, 18171905, 24260284). As a result, alleles having c.516G>T are considered decreased function, regardless of the functional status of additional other variants unless these cause no function (e.g., CYP2B6*13 and CYP2B6*38). A single in vitro study reported decreased function for p.R140W using buproprion and efavirez as probes (38596098). Therefore, the consensus among experts was decreased function based on the presence of c.516G>T and limited evidence.	{"Latino": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
777595	344	CYP2C19	*35	\N	No function	\N	\N	777594	{26021325}	Limited	\N	CYP2C19*35 is assigned no function based on limited evidence. CYP2C19*35 is defined by a splicing defect resulting in a truncated protein (26021325). This splicing defect is also found in CYP2C19*2 which definitively has no function. Although subjects with CYP2C19 *1/*35 did not demonstrate significantly decreased enzyme activity compared to wildtype based on urine metabolites after mephenytoin 100mg once (26021325), the experts did not find this result convincing due to the small sample size. Therefore, consensus among experts was no function based on limited evidence as it was determined the phenotypes containing this allele would be clinically distinct from phenotypes comprising normal function and decreased function alleles.	{"Latino": null, "American": null, "European": 0.0, "Oceanian": null, "East Asian": 0.0, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": 0.032099508, "African American/Afro-Caribbean": 0.015904458}	f
777691	344	CYP2C9	*12	Decreased function	Decreased function	\N	0.5	777690	{15284535,23752738,28758225,23688605}	Limited	\N	CYP2C9*12 is assigned decreased function based on limited evidence in heterozygous patients and in vitro studies. Four patients on a stable dose of warfarin with CYP2C9*1/*12 genotype required a lower weekly warfarin dose compared to CYP2C9*1/*1 patients (23688605). In vitro studies similarly found CYP2C9*12 demonstrated decreased enzyme activity with warfarin and tolbutamide substrates compared to wildtype (23752738, 15284535, 28758225). Therefore, consensus among experts was decreased function with an activity value of 0.5 based on limited evidence as it was determined the phenotypes containing this allele would be clinically distinct from phenotypes comprising normal function alleles.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": 0.00041809047, "Near Eastern": 0.001, "Central/South Asian": 0.0, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.0}	f
779705	283	CYP2D6	*10x2	\N	Decreased function	\N	0.5	777954	{15149890}	Limited	\N	CYP2D6*10x2 is assigned decreased function based on limited evidence. Three subjects with CYP2D6*10/*10x2 genotype demonstrated similar dextromethorphan metabolism compared to CYP2D6*10/*10 subjects and decreased metabolism compared to CYP2D6 *1/*1, CYP2D6 *1/*2, and CYP2D6*1/*10 subjects based on urine metabolites (15149890). Therefore, consensus among experts was decreased function with an activity value of 0.5 based on limited evidence as it was determined the phenotypes containing this allele would be clinically distinct from phenotypes comprising normal function alleles and clinically similar to phenotypes comprising decreased function alleles.	{"Latino": 0.0016659324, "American": 0.0, "European": 0.0001068211, "Oceanian": 0.0, "East Asian": 0.005851049, "Near Eastern": 0.0022595506, "Central/South Asian": 0.0, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.0011707664}	f
778051	340	CYP2D6	*59	\N	Decreased function	\N	0.5	778050	{17001296,26335396}	Moderate	\N	CYP2D6*59 is assigned decreased function based on moderate evidence. CYP2D6*59 has been described in subjects demonstrating decreased sparteine and dextromethorphan metabolism (17001296, 26335396). An in vitro study found CYP2D6*59 exhibited decreased mRNA levels and enzyme activity with a propafenone substrate compared to wildtype (17001296). Therefore, consensus among experts was decreased function with an activity value of 0.5 based on moderate evidence.	{"Latino": null, "American": 0.001, "European": 0.003719603, "Oceanian": null, "East Asian": 0.0, "Near Eastern": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.0}	f
778795	296	G6PD	Chikugo	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778794	{22293322,1945893}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
3685809	135	RYR1	c.11518G>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685808	{35849058}	\N	\N	None	{"Latino": null, "American": null, "European": 0.0000294, "East Asian": 0.0003846, "Near Eastern": null, "Central/South Asian": 0.0002072, "Sub-Saharan African": 0.000145}	f
779292	322	SLCO1B1	*8	\N	Uncertain function	\N	\N	779291	{11477075,12490595}	Inadequate	\N	SLCO1B1*8 is assigned uncertain function based on in vitro studies demonstrating unaltered uptake of estrone sulfate, estradiol 17beta-d-glucuronide and rifampin (11477075, 12490595), but no clinical data. Therefore, consensus among experts was uncertain function due to inadequate evidence.	{"American": null, "European": 0.0, "Oceanian": null, "East Asian": 0.0, "Near Eastern": null, "Central/South Asian": 0.0, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778169	339	CYP2D6	*125	\N	Unknown function	\N	n/a	778168	{}	No Evidence	\N	CYP2D6*125 is assigned unknown function due to no literature describing function of this allele. Therefore, consensus among experts was unknown function due to no available evidence.	{"Latino": null, "American": 0.0, "European": 0.0, "Oceanian": null, "East Asian": 0.0, "Near Eastern": null, "Central/South Asian": 0.0, "Sub-Saharan African": 0.003, "African American/Afro-Caribbean": 0.003}	f
778979	296	G6PD	Georgia	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778978	{22293322,7803800}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
777729	344	CYP2C9	*31	Decreased function	Decreased function	\N	0.5	777728	{23752738,24118918,23844998,25142737,25144335,25951663,25476996,25832633,25884291,25924705,27163851,27199745,24077631}	Limited	\N	CYP2C9*31 is assigned decreased function based on limited evidence. Multiple in vitro studies using different cell systems found CYP2C9*31 demonstrated decreased clearance for numerous substrates compared to wildtype (23752738, 24118918, 23844998, 25144335, 25951663, 25476996, 25832633, 25884291, 27163851, 25924705, 27199745, 24077631). Although one in vitro study showed CYP2C9*31 had similar activity compared to wildtype, the experts did not find this result convincing as in this study CYP2C9*2 and CYP2C9*3 which definitively have decreased function and no function, respectively, demonstrated increased activity compared to wildtype (25142737). Therefore, consensus among experts was decreased function with an activity value of 0.5 based on limited evidence as it was determined the phenotypes containing this allele would be clinically distinct from phenotypes comprising normal function alleles.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": 0.0016030075, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
777999	340	CYP2D6	*33	\N	Normal function	\N	1.0	777998	{9241659,24647041,30366777}	Limited	\N	CYP2D6*33 is assigned normal function based on limited evidence. CYP2D6*33 was first described in a subject with CYP2D6 *5/*33 genotype demonstrating similar sparteine metabolism compared to CYP2D6 *1/*5 and CYP2D6 *2/*5 subjects, indicating normal enzyme activity (9241659). In vitro studies similarly found CYP2D6*33 had normal enzyme activity and similar intrinsic clearance compared to wildtype with various substrates (24647041, 30366777). Therefore, consensus among experts was normal function with an activity value of 1 based on limited evidence as it was determined the phenotypes containing this allele would be clinically similar to phenotypes comprising normal function alleles.	{"Latino": null, "American": 0.0022216009, "European": 0.009507331, "Oceanian": null, "East Asian": 0.00021425438, "Near Eastern": 0.0, "Central/South Asian": 0.002, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.0}	f
3827873	117	MT-RNR1	m.663A>G	\N	uncertain risk of aminoglycoside-induced hearing loss	\N	\N	3827872	{8414970,7689389,7550368}	Inadequate evidence	\N	MT-RNR1 663A>G is assigned an uncertain risk of aminoglycoside-induced hearing loss based on inadequate evidence. This variant has been identified in individuals with aminoglycoside-induced hearing loss but also in controls after aminoglycoside exposure (8414970, 7689389, 7550368). Therefore, consensus among experts is that there is uncertain risk of aminoglycoside-induced hearing loss associated with this variant.	{"European": 0.0014543316, "East Asian": 0.04993, "Near Eastern": 0.0, "Central/South Asian": 0.003349, "Sub-Saharan African": null}	f
778179	339	CYP2D6	*130	\N	Uncertain function	\N	n/a	778178	{32759992}	Inadequate	\N	CYP2D6*130 is assigned uncertain function due to inadequate literature describing function of this allele. One in vitro study demonstrated substantially decreased intrinsic clearance CLint (Vmax/Km) of 3.2% compared to *1 for tamoxifen N-desmethylation; no activity was detectable for dextromethorphan O-demethylation (32759992). Therefore, consensus among experts was uncertain function due to inadequate evidence.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778711	296	G6PD	Hechi	II/Deficient	II/Deficient	\N	\N	778710	{22293322,17018380}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
778823	296	G6PD	Mexico City	III/Deficient	III/Deficient	\N	\N	778822	{22293322,1611091}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": 0.00018234865, "European": 0.000040952138, "East Asian": 0.0, "Central/South Asian": 0.0, "African American/Afro-Caribbean": 0.0}	f
3685407	135	RYR1	c.1202G>T	Likely Pathogenic	Malignant Hyperthermia associated	\N	n/a	3685406	{35849058}	\N	\N	PS4_Mod, PM1_Sup, PM5, PP1, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685439	135	RYR1	c.1615T>C	Likely Pathogenic	Malignant Hyperthermia associated	\N	n/a	3685438	{35849058}	\N	\N	PS4_Mod, PM1, PP1, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
778751	296	G6PD	A- 968C_376G	III/Deficient	III/Deficient	\N	\N	778750	{22293322,32387609,2572288}	strong	\N	Function assigned based on the WHO recommendations included in PMID 22293322. Additional in vitro (32387609) and the presence of this variant in G6PD deficient males (2572288) supports this classificaiton.	{"Latino": 0.0007489835, "European": 0.0, "East Asian": 0.0, "Central/South Asian": 0.0, "African American/Afro-Caribbean": 0.0054458817}	f
3685657	135	RYR1	c.7310C>T	Likely Pathogenic	Malignant Hyperthermia associated	\N	n/a	3685656	{35849058}	\N	\N	PS4_Mod, PM1, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
779294	323	SLCO1B1	*9	Decreased function	No function	\N	\N	779293	{11477075,12490595,16697742,16513443,33658230,40047317,39644095}	Moderate	\N	SLCO1B1*9 is assigned no function based on moderate evidence. SLCO1B1*9 is defined by c.1463G>C (p.G488A). In vitro studies demonstrate that protein encoded by SLCO1B1*9 exhibits decreased uptake of estrone sulfate, estradiol 17beta-d-glucuronide, rifampin, rosuvastatin, methotrexate, and atrasentan (11477075, 12490595, 16697742, 16513443, 40047317). A large clinical study demonstrated that individuals with the c.1463G>C variant exhibited significantly increased bilirubin levels relative to those without. Additionally, c.1463G>C was significantly associated with statin-induced myotoxicity (40047317) and has been linked to altered oxylipin levels (39644095). Since c.1463G>A is in strong linkage with c.388A>G (p.N130D) in African populations, the association study (40047317) likely included subjects with either the SLCO1B1*9 or *31 allele Nine out of ten variant effect predictors tested by CPIC staff predict that the SLCO1B1*9-defining variant, c.1463G>C (p.G488A), impairs protein function.	{"American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
779348	322	SLCO1B1	*36	\N	Uncertain function	\N	\N	779347	{22147369}	Inadequate	\N	SLCO1B1*35 is assigned uncertain function based on no in vitro evidence and limited clinical data. One clinical study showed no statistical difference in methotrexate clearance (22147369). Therefore, consensus among experts was uncertain function due to inadequate evidence.	{"American": null, "European": 0.0, "Oceanian": null, "East Asian": 0.0, "Near Eastern": null, "Central/South Asian": 0.0, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
779421	322	TPMT	*13	\N	Uncertain function	\N	\N	779420	{18708949,13679074,16220112}	\N	\N	\N	{"Latino": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
779298	322	SLCO1B1	*11	\N	Uncertain function	\N	\N	779297	{11477075,12490595}	Inadequate	\N	SLCO1B1*11 is assigned uncertain function based on in vitro studies demonstrating reduced uptake of rifampin (12490595), but not of estrone sulfate or estradiol 17beta-d-glucuronide (11477075) and no clinical data. Therefore, consensus among experts was uncertain function due to inadequate evidence.	{"American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
777955	340	CYP2D6	*10	\N	Decreased function	\N	0.25	777954	{8764380,11266079,18784265,8287064,24647041,25469868,26310775,26542054,26652007,26937172,26968424,27203132,27251229,27354764,27538917,19364831,30366777,31647186}	Strong	\N	CYP2D6*10 is assigned decreased function based on strong evidence. CYP2D6*10 has consistently been described in subjects demonstrating decreased metabolism of various CYP2D6 substrates, with metabolic ratios greater than those observed in wildtype subjects but less than poor metabolizers (8764380, 8287064, 19364831). In vitro studies using different cell systems similarly found CYP2D6*10 demonstrates decreased intrinsic clearance compared to wildtype with various substrates (27538917, 27354764, 27251229, 27203132, 26968424, 26937172, 26652007, 26542054, 26310775, 25469868, 30366777, 24647041, 11266079, 18784265). As part of the standardization of CYP2D6 genotype to phenotype translation among CPIC and the Dutch Pharmacogenetics Working Group, CYP2D6*10 was reevaluated as the evidence suggests the activity of the CYP2D6*10 is considerably lower compared to other decreased function alleles and the activity value of 0.5 (previously assigned) may overestimate metabolic capacity of patients with this allele (31647186). Therefore, consensus among experts was decreased function with an activity value of 0.25 based on strong evidence.	{"Latino": 0.026291614, "American": 0.014500251, "European": 0.01571283, "Oceanian": 0.05713253, "East Asian": 0.4284454, "Near Eastern": 0.06769364, "Central/South Asian": 0.07559443, "Sub-Saharan African": 0.048626088, "African American/Afro-Caribbean": 0.038160447}	f
110056	127	HLA-B	*57:01	\N	\N	\N	\N	9002	\N	\N	\N	\N	{"Latino": 0.013904181, "American": 0.024912989, "European": 0.036044996, "Oceanian": 0.015734065, "East Asian": 0.009806251, "Near Eastern": 0.02337437, "Central/South Asian": 0.06814844, "Sub-Saharan African": 0.006092622, "African American/Afro-Caribbean": 0.006087779}	f
3685511	135	RYR1	c.5183C>T	Likely Pathogenic	Malignant Hyperthermia associated	\N	n/a	3685510	{33767344}	\N	\N	PS4, PP1_St, BP4	{"Latino": null, "American": null, "European": 0.0000294, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685599	135	RYR1	c.7035C>A	Likely Pathogenic	Malignant Hyperthermia associated	\N	n/a	3685598	{35849058}	\N	\N	PS3_Mod, PS4_Mod, PM1	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685769	135	RYR1	c.10042C>T	Variant of uncertain significance	Uncertain function	\N	n/a	3685768	{33767344}	\N	\N	PS4_Sup	{"Latino": null, "American": null, "European": 0.0001617, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": 0.00002412}	f
777437	344	CYP2B6	*8	No function	No function	\N	\N	777436	{14551287,15190123,20517174,21659470,21746968,30201214}	Limited	\N	CYP2B6*8 (c.415A>G, p.K139E) - No function: CYP2B6*8 is assigned no function. Multiple in vitro studies using human liver microsomes (14551287) and cDNA expression systems (15190123, 20517174, 21659470, 21746968, 30201214) found that CYP2B6*8 had no enzyme activity compared to the *1 reference with various substrates. Therefore, consensus among experts was no function based on limited evidence.	{"Latino": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": 0.0}	f
1406320	326	CYP2C9	*74	Unknown function	Unknown function	\N	n/a	1406319	{}	No evidence	\N	CYP2C9*74 is assigned unknown function due to no literature describing function of this allele. Therefore, consensus among experts was unknown function due to no available evidence.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778111	340	CYP2D6	*96	\N	No function	\N	0.0	778110	{25469868,26310775,26666748,26544071,26406933,27109434,27097346,27016952,26542054,26937172,26968424,27203132,27251229,27354764,27538917}	Limited	\N	CYP2D6*96 is assigned no function based on limited evidence. Multiple in vitro studies found CYP2D6*96 had nondetectable enzyme with various substrates (25469868, 26310775, 26666748, 26544071, 26406933, 27109434, 27097346, 27016952, 26542054, 26937172, 26968424, 27203132, 27251229, 27354764, 27538917). CYP2D6*96 is defined by an early stop codon yielding a truncated nonfunctional protein. Therefore, consensus among experts was no function with an activity value of 0 based on limited evidence.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
2091257	244	CYP2D6	*162	\N	Uncertain function	\N	n/a	2091256	{}	Inadequate	\N	CYP2D6*162 is assigned uncertain function based on inadequate evidence. CYP2D6*162 is defined by the two SNPs defining the normal function *2 allele and the SNP defining the normal function *27 allele.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": 0.00052, "African American/Afro-Caribbean": null}	f
779447	322	TPMT	*26	\N	Uncertain function	\N	\N	779446	{19660010}	\N	\N	\N	{"Latino": 0.0, "European": 0.0, "East Asian": 0.0003479, "Near Eastern": null, "Central/South Asian": 0.0, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
777469	343	CYP2B6	*25	\N	Uncertain function	\N	\N	777468	{20517174,21746968,30201214}	Inadequate	\N	CYP2B6*25 (c.1454A>T, p.Q485L) – Uncertain function: CYP2B6*25 is assigned uncertain function. In vitro studies using cDNA expression systems showed no significant changes in enzyme activity and/or protein expression compared to the *1 reference (20517174, 21746968, 30201214). However, there were no in vivo data available or data in human liver microsomes. Therefore, consensus among experts was uncertain function based on inadequate evidence.	{"Latino": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
2899155	133	CYP2B6	*45	\N	Uncertain function	\N	\N	2899154	{38596098}	Inadequate	\N	CYP2B6*45 (c.547G>A, p.V183I) – Uncertain function: CYP2B6*45 is assigned uncertain function due to inadequate evidence describing function. A single in vitro study reported decreased function for p.V183I using buproprion and efavirez as probes (38596098).	{"Latino": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778109	340	CYP2D6	*95	\N	Uncertain function	\N	n/a	778108	{25469868,26310775,26666748,26544071,26406933,27109434,27097346,27016952,26542054,26937172,26968424,27203132,27251229,27354764,27538917}	Inadequate	\N	CYP2D6*95 is assigned uncertain function due to inadequate evidence. In vitro studies found CYP2D6*95 demonstrated enzyme activity ranging from similar to decreased activity compared to wildtype with various substrates (25469868, 26310775, 26666748, 26544071, 26406933, 27109434, 27097346, 27016952, 26542054, 26937172, 26968424, 27203132, 27251229, 27354764, 27538917). Therefore, consensus among experts was uncertain function.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778151	339	CYP2D6	*116	\N	Unknown function	\N	n/a	778150	{}	No Evidence	\N	CYP2D6*116 is assigned unknown function due to no literature describing function of this allele. Therefore, consensus among experts was unknown function due to no available evidence.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778187	339	CYP2D6	*134	\N	Uncertain function	\N	n/a	778186	{32759992}	Inadequate	\N	CYP2D6*134 is assigned uncertain function due to inadequate literature describing function of this allele. One in vitro study demonstrated intrinsic clearance CLint (Vmax/Km) of 104.5% and 81.2 % compared to *1 for tamoxifen N-desmethylation and dextromethorphan O-demethylation, respectively, suggesting normal activity (32759992). Therefore, consensus among experts was uncertain function due to inadequate evidence.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778418	327	DPYD	c.1627A>G (*5)	Normal function	Normal function	\N	1.0	778417	{23328581}	Strong	\N	5-fluorouracil (in vitro)	{"Latino": 0.3070716, "European": 0.19492984, "East Asian": 0.25466427, "Central/South Asian": 0.09372777, "Sub-Saharan African": 0.157875, "African American/Afro-Caribbean": 0.14005096}	f
3685775	135	RYR1	c.10100A>G	Likely Benign	Normal function	\N	n/a	3685774	{35849058}	\N	\N	BS3_Sup	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
778997	296	G6PD	Hermoupolis	II/Deficient	II/Deficient	\N	\N	778996	{22293322,10782016}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
778907	296	G6PD	Ierapetra	II/Deficient	II/Deficient	\N	\N	778906	{22293322,1611091}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
778985	296	G6PD	Mediterranean Haplotype	II/Deficient	II/Deficient	\N	\N	778984	{22293322,1978554}	Inadequate	\N	Based on function of the 563T variant, present in the Mediterranean, Dallas, Panama‚ Sassari, Cagliari, Birmingham, function was assigned as WHO class II (22293322, 1978554).	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
2899159	133	CYP2B6	*47	\N	Uncertain function	\N	\N	2899158	{38596098}	Inadequate	\N	CYP2B6*47 (c.1060_1061delinsCG, p.Y354R) – Uncertain function: CYP2B6*47 is assigned uncertain function due to inadequate evidence describing function. A single in vitro study reported decreased function for p.Y354R using buproprion and efavirez as probes (38596098).	{"Latino": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
779029	296	G6PD	Split	III/Deficient	III/Deficient	\N	\N	779028	{22293322,16143877}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
778787	296	G6PD	Volendam	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778786	{22293322,10556177}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
777559	344	CYP2C19	*14	\N	Uncertain function	\N	\N	777558	{21325430,25001882,21692664}	Inadequate	\N	CYP2C19*14 is assigned uncertain function due to inadequate evidence. CYP2C19*14 demonstrated similar enzyme activity compared to wildtype with mephenytoin, omeprazole, and other substrates (21325430, 21692664). In a separate in vitro study CYP2C19*14 demonstrated decreased activity compared to wildtype with mephenytoin and clopidogrel substrates (25001882). Therefore, consensus among experts was not achieved and uncertain function was assigned.	{"Latino": 0.0, "American": 0.0, "European": 0.0, "Oceanian": null, "East Asian": 0.0001145213, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.0}	f
777789	344	CYP2C9	*61	Decreased function	Decreased function	\N	0.5	777788	{30518301}	Limited	\N	CYP2C9*61 is assigned decreased function based on limited evidence in a heterozygous patient. CYP2C9*61 was first described in a patient requiring a low daily warfarin dose of 3mg (30518301). CYP2C9*61 is defined by two SNPs, one of which is the defining SNP for CYP2C9*2. Therefore, consensus among experts was decreased function with an activity value of 0.5 based on limited evidence as it was determined the function of this allele is similar to CYP2C9*2 and phenotypes containing this allele would be clinically distinct from phenotypes comprising normal function alleles.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778436	325	DPYD	c.1905C>G	Normal function	Normal function	\N	1.0	778435	{24648345}	Limited	\N	5-fluorouracil (in vitro)	{"Latino": 0.0, "European": 0.000054979286, "East Asian": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.0}	f
778999	296	G6PD	Harima	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778998	{22293322,1945893}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
778861	296	G6PD	Mizushima	II/Deficient	II/Deficient	\N	\N	778860	{22293322,7705842}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
778883	296	G6PD	Nara	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778882	{22293322,8241497}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
778949	296	G6PD	Nashville, Anaheim, Portici	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778948	{22293322,16934959,1999409,1536798}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
777771	344	CYP2C9	*52	No function	No function	\N	0.0	777770	{24077631,24118918,25142737,25144335,25476996,25832633,25951663,25884291,25924705,27163851,23844998}	Limited	\N	CYP2C9*52 is assigned no function based on limited evidence in in vitro studies. Multiple in vitro studies found CYP2C9*52 demonstrated markedly decreased clearance compared to wildtype with various substrates (24077631, 24118918, 25142737, 25144335, 25476996, 25832633, 25951663, 25884291, 25924705, 27163851, 23844998). Therefore, consensus among experts was no function with an activity value of 0 based on limited evidence as it was determined the phenotypes containing this allele would be clinically distinct from phenotypes comprising normal function or decreased function alleles.	{"Latino": 0.0, "American": null, "European": 0.0, "Oceanian": null, "East Asian": null, "Near Eastern": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
777803	326	CYP2C9	*68	Uncertain function	Uncertain function	\N	n/a	777802	{33536773}	Inadequate evidence	\N	CYP2C9*68 is assigned uncertain funciton due to inadequate evidence. The nonsynonymous variants present in CYP2C9*68 are predicted to be deleterious in SIFT and and benign in Polyphen predictions. There are no in vitro or clinical studies reported. Consensus was not achieved among experts and therefore uncertain function was assigned.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778199	246	CYP2D6	*140	\N	Unknown function	\N	n/a	778198	{}	No Evidence	\N	CYP2D6*140 is assigned unknown function due to no literature describing function of this allele. Therefore, consensus among experts was unknown function due to no available evidence.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778406	327	DPYD	c.1484A>G	No function	No function	\N	0.0	778405	{24648345}	Limited	\N	5-fluorouracil (in vitro)	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778811	296	G6PD	Dagua	Uncertain	Uncertain function	\N	\N	778810	{22293322}	Inadequate	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": 0.0, "European": 0.0, "East Asian": 0.0, "Central/South Asian": 0.000104821804, "African American/Afro-Caribbean": 0.0}	f
778757	296	G6PD	Vanua Lava	II/Deficient	II/Deficient	\N	\N	778756	{22293322,3591235}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": 0.0, "European": 0.0, "East Asian": 0.0, "Central/South Asian": 0.0, "African American/Afro-Caribbean": 0.0}	f
779235	323	RYR1	c.14477C>T	Pathogenic	Malignant Hyperthermia associated	\N	n/a	779234	{33767344}	\N	\N	PS3, PS4, PM1_Sup, PP1_St, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
779239	323	RYR1	c.14512C>G	Likely Pathogenic	Malignant Hyperthermia associated	\N	n/a	779238	{33767344}	\N	\N	PS3_Sup, PS4_Mod, PM1_Sup, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
778937	296	G6PD	Guadalajara	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778936	{22293322,32387609,7129446}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
778905	296	G6PD	Partenope	II/Deficient	II/Deficient	\N	\N	778904	{22293322}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
778981	296	G6PD	Surabaya	II/Deficient	II/Deficient	\N	\N	778980	{22293322,11499668}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": 0.000036485697, "European": 0.0, "East Asian": 0.0, "Central/South Asian": 0.0, "African American/Afro-Caribbean": 0.0}	f
778977	296	G6PD	Tokyo, Fukushima	I-II/Deficient with CNSHA-Deficient	I/Deficient with CNSHA	\N	\N	778976	{22293322,28028996,7440223,9192788,1733837}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
778765	296	G6PD	Valladolid	II/Deficient	II/Deficient	\N	\N	778764	{22293322,9332310}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
3685353	135	RYR1	c.496G>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685352	{35849058}	\N	\N	PS4_Mod, PM1	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685357	135	RYR1	c.526G>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685356	{35849058}	\N	\N	PS4_Mod, PM1	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": 0.0000483}	f
3685363	135	RYR1	c.533A>G	Likely Pathogenic	Malignant Hyperthermia associated	\N	n/a	3685362	{35849058}	\N	\N	PS2_PM6_Mod, PS4_Sup, PM1, PP1, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
777561	344	CYP2C19	*15	\N	Normal function	\N	\N	777560	{21325430,25001882}	Limited	\N	CYP2C19*15 is assigned normal function based on limited evidence. Two in vitro studies using different cell systems found CYP2C19*15 demonstrated similar enzyme activity compared to wildtype with mephenytoin and omeprazole substrates (21325430, 25001882). Therefore, consensus among experts was normal function based on limited evidence as it was determined the phenotypes containing this allele would be clinically similar to phenotypes comprising normal function alleles.	{"Latino": 0.004, "American": null, "European": 0.002, "Oceanian": null, "East Asian": 0.0013589837, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": 0.052882355, "African American/Afro-Caribbean": 0.014}	f
777573	344	CYP2C19	*23	\N	Uncertain function	\N	\N	777572	{25001882,27578295,30464555,31713493}	Inadequate	\N	CYP2C19*23 is assigned uncertain function due to inadequate evidence. In vitro studies found CYP2C19*23 demonstrated enzyme activity ranging from decreased to increased compared to wildtype with various substrates (25001882, 27578295, 30464555, 31713493). Therefore, consensus among experts was uncertain function due to inadequate evidence.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": 0.00056672905, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
777585	344	CYP2C19	*30	\N	Uncertain function	\N	\N	777584	{26153442,30464555,29098786}	Inadequate	\N	CYP2C19*30 is assigned uncertain function due to inadequate evidence. In vitro studies found CYP2C19*30 demonstrated decreased enzyme activity compared to wildtype with mephenytoin, omeprazole, voriconazole, and nebivolol substrates (26153442, 30464555, 29098786). Consensus was not achieved among experts as data were sparse. Therefore, uncertain function was assigned.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": 0.00019440125, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778901	296	G6PD	Chinese-5	III/Deficient	III/Deficient	\N	\N	778900	{22293322,8471773}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": 0.0, "European": 0.0, "East Asian": 0.0016838418, "Central/South Asian": 0.0, "African American/Afro-Caribbean": 0.000052534804}	f
778841	296	G6PD	Cleveland Corum	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778840	{22293322,7803800,7577654}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
778893	296	G6PD	Villeurbanne	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778892	{22293322,22139979}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
779741	282	CYP2D6	*41x3	\N	Decreased function	\N	0.75	778014	{11037799,15289790,17001295,17112815,19364831}	Limited	\N	CYP2D6*41x3 is assigned decreased function based on limited evidence. CYP2D6*41 is assigned decreased function based on decreased protein expression and enzyme activity (11037799, 15289790, 17112815, 19364831, 17001295). Therefore, consensus among experts was decreased function with an activity value of 0.75 based on limited evidence as it was determined the phenotypes containing a duplication of this allele would demonstrate greater protein expression and enzyme activity than that of the nonduplicated allele and be clinically similar to phenotypes comprising decreased function alleles.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778995	296	G6PD	Cassano	II/Deficient	II/Deficient	\N	\N	778994	{22293322,8447319,10782016}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
3685375	135	RYR1	c.680A>T	Variant of uncertain significance	Uncertain function	\N	n/a	3685374	{35849058}	\N	\N	PS4_Sup, PM1, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685747	135	RYR1	c.9356G>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685746	{35849058}	\N	\N	None	{"Latino": null, "American": null, "European": null, "East Asian": 0.0001925, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": 0.00002412}	f
3685753	135	RYR1	c.9649T>C	Variant of uncertain significance	Uncertain function	\N	n/a	3685752	{35849058}	\N	\N	PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685931	135	RYR1	c.14510delA	Likely Benign	Normal function	\N	n/a	3685930	{35849058}	\N	\N	PS4_Sup, BS2_Mod, BS3_Sup	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
1002696	316	SLCO1B1	*42	\N	Uncertain function	\N	\N	1002695	{33658230}	Inadequate	\N	SLCO1B1*42 is assigned uncertain function based on limited in vitro evidence. It contains two variants, rs2306283 and rs141467543. One in vitro study found normal protein expression and transport for the rs141467543 variant (33658230). Therefore, consensus among experts was uncertain function due to inadequate evidence.	{"American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
777679	344	CYP2C9	*6	No function	No function	\N	0.0	777678	{23752738,15289788,11740344,16220110,17895500,21811894,15094935}	Strong	\N	CYP2C9*6 is assigned no function based on strong supporting evidence in heterozygous and homozygous patients. This allele was first identified in a CYP2C9*6/*6 patient experiencing phenytoin toxicity after recently starting the medication. Based on serial phenytoin plasma concentrations after discontinuing phenytoin, the patient had an estimated 17% phenytoin clearance compared to wildtype (11740344). In a separate case report, a patient with CYP2C9*6/*6 genotype stable on a low weekly warfarin dose demonstrated impaired warfarin metabolism with an S:R warfarin ratio 6x greater than expected (15094935). The S:R warfarin ratio of this patient was the highest among 52 patients on a stable dose of warfarin with a CYP2C9 genotype of *1/*1, *1/*2, *1/*3, *2/*2, or *2/*3 (17895500). Two subjects (CYP2C9*1/*6 and CYP2C9*5/*6 genotype, respectively) had decreased losartan metabolism compared to wildtype subjects based on urinary metabolites after a single 25mg dose (15289788). Three CYP2C9*1/*6 subjects and one CYP2C9*5/*6 subjects had lower phenytoin metabolism compared to wildtype based on urinary excretion of a phenytoin metabolite after a single 300mg dose. Additionally, the CYP2C9*5/*6 subject demonstrated the lowest phenytoin metabolism as the only subject of the 109 subject cohort to have a urinary metabolite concentration below the limit of quantification (16220110). CYP2C9*6 is defined by a deletion resulting in a frameshift and not included in in vitro studies as it is it is a null allele resulting in no protein formation (23752738). Although one CYP2C9*1/*6 subject had a similar acenocoumarol metabolite plasma concentration compared to wildtype subjects 8 and 24 hours after a single 8mg dose (21811894), the experts did not deem this result as convincing conflicting evidence based on the small sample size. Therefore, consensus among experts was no function with an activity value of 0 based on strong evidence.	{"Latino": 0.0009750473, "American": 0.0, "European": 0.00028025627, "Oceanian": null, "East Asian": 0.0, "Near Eastern": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": 0.008801762, "African American/Afro-Caribbean": 0.008521383}	f
778368	331	DPYD	c.967G>A	Normal function	Normal function	\N	1.0	778367	{24648345}	Limited	\N	5-fluorouracil (in vitro)	{"Latino": 0.0, "European": 0.000041703854, "East Asian": 0.0, "Central/South Asian": 0.00017881511, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.0}	f
3685321	135	RYR1	c.131G>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685320	{35849058}	\N	\N	PS4_Sup, PM1, PP3_Mod	{"Latino": null, "American": null, "European": 0.0000147, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685323	135	RYR1	c.152C>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685322	{33767344}	\N	\N	PM1	{"Latino": null, "American": null, "European": 0.0001323, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": 0.00002413}	f
3685387	135	RYR1	c.992_994dup	Variant of uncertain significance	Uncertain function	\N	n/a	3685386	{35849058}	\N	\N	PS4_Sup, PM1	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685443	135	RYR1	c.1630G>T	Likely Pathogenic	Malignant Hyperthermia associated	\N	n/a	3685442	{35849058}	\N	\N	PS4_Sup, PM1, PP1, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685503	135	RYR1	c.5024T>C	Variant of uncertain significance	Uncertain function	\N	n/a	3685502	{35849058}	\N	\N	PS4_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685517	135	RYR1	c.5341T>C	Variant of uncertain significance	Uncertain function	\N	n/a	3685516	{35849058}	\N	\N	PS4_Sup, BP4	{"Latino": null, "American": null, "European": 0.00002941, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
778338	331	DPYD	c.295_298delTCAT (*7)	No function	No function	\N	0.0	778337	{24648345}	Moderate	\N	5-fluorouracil (in vitro)	{"Latino": 0.00010, "European": 0.00018195312, "East Asian": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778336	329	DPYD	c.85T>C (*9A)	Normal function	Normal function	\N	1.0	778335	{18452418}	Strong	\N	Dihydrouracil (in vivo)	{"Latino": 0.20892397, "European": 0.22749932, "East Asian": 0.076328315, "Central/South Asian": 0.25525716, "Sub-Saharan African": 0.4464008, "African American/Afro-Caribbean": 0.42713377}	f
778358	329	DPYD	c.703C>T (*8)	No function	No function	\N	0.0	778357	{24648345}	Moderate	\N	5-fluorouracil (in vitro)	{"Latino": 0.0, "European": 0.00009098349, "East Asian": 0.0, "Central/South Asian": 0.00020, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
3685705	135	RYR1	c.7879G>C	Likely Pathogenic	Malignant Hyperthermia associated	\N	n/a	3685704	{35849058}	\N	\N	PS4_Mod, PP1_St, PP3_Mod	{"Latino": null, "American": null, "European": 0.00001471, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685339	135	RYR1	c.463C>A	Likely Pathogenic	Malignant Hyperthermia associated	\N	n/a	3685338	{35849058}	\N	\N	PS3_Mod, PM1, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685691	135	RYR1	c.7760A>G	Variant of uncertain significance	Uncertain function	\N	n/a	3685690	{35849058}	\N	\N	PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685749	135	RYR1	c.9499C>T	Variant of uncertain significance	Uncertain function	\N	n/a	3685748	{35849058}	\N	\N	None	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685779	135	RYR1	c.10237A>T	Variant of uncertain significance	Uncertain function	\N	n/a	3685778	{35849058}	\N	\N	PS4_Sup, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685783	135	RYR1	c.10556C>T	Variant of uncertain significance	Uncertain function	\N	n/a	3685782	{33767344}	\N	\N	None	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685793	135	RYR1	c.11086G>C	Variant of uncertain significance	Uncertain function	\N	n/a	3685792	{35849058}	\N	\N	PS4_Sup	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685795	135	RYR1	c.11120G>T	Variant of uncertain significance	Uncertain function	\N	n/a	3685794	{35849058}	\N	\N	PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685837	135	RYR1	c.12149C>A	Likely Pathogenic	Malignant Hyperthermia associated	\N	n/a	3685836	{35849058}	\N	\N	PS4_Mod, PP1_St, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
777963	340	CYP2D6	*14	\N	Decreased function	\N	0.5	777962	{18784265,19364831,24647041,30366777}	Limited	\N	CYP2D6*14 is assigned decreased function based on limited evidence. Three subjects with CYP2D6*1/*14, CYP2D6 *10/*14, and CYP2D6*14/*41 genotype, respectively demonstrated decreased dextromethorphan metabolism compared to wildtype based on urine metabolites (19364831). Multiple in vitro studies found CYP2D6*14 had modestly decreased enzyme activity compared to wildtype with various substrates (18784265, 19364831, 24647041, 30366777). Therefore, consensus among experts was decreased function with an activity value of 0.5 based on limited evidence as it was determined the phenotypes containing this allele would be clinically distinct from phenotypes comprising normal function alleles.	{"Latino": 0.0, "American": 0.0, "European": 0.0, "Oceanian": 0.0, "East Asian": 0.004713944, "Near Eastern": null, "Central/South Asian": 0.0, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.0}	f
777969	340	CYP2D6	*18	\N	No function	\N	0.0	777968	{8946471,10471060,18784265,24647041,30366777}	Moderate	\N	CYP2D6*18 is assigned no function based on moderate evidence. CYP2D6*18 is defined by a 9 base insertion yielding a nonfunctional enzyme and has been described in subjects demonstrating markedly decreased metabolism of sparteine and debrisoquine (8946471, 10471060). Multiple in vitro studies found CYP2D6*18 had decreased enzyme activity compared to wildtype with various substrates (8946471, 18784265, 24647041, 30366777). Therefore, consensus among experts was no function with an activity value of 0 based on moderate evidence.	{"Latino": null, "American": null, "European": 0.0, "Oceanian": null, "East Asian": 0.0013486103, "Near Eastern": 0.0, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": 0.0}	f
777971	339	CYP2D6	*19	\N	No function	\N	0.0	777970	{9241659}	Limited	\N	CYP2D6*19 is assigned no function based on limited evidence. CYP2D6*19 is defined by a four base deletion resulting in a frameshift and yielding a nonfunctional enzyme (9241659). Therefore, consensus among experts was no function with an activity value of 0 based on limited evidence as it was determined the phenotypes containing this allele would be clinically distinct from phenotypes comprising normal and decreased function alleles.	{"Latino": null, "American": null, "European": 0.0003139269, "Oceanian": 0.002224, "East Asian": 0.0, "Near Eastern": 0.0, "Central/South Asian": null, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.0}	f
778370	327	DPYD	c.1003G>T (*11)	Normal function	Normal function	\N	1.0	778369	{24648345}	Moderate	\N	5-fluorouracil (in vitro)	{"Latino": 0.0, "European": 0.0, "East Asian": 0.00010, "Central/South Asian": 0.0, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778925	296	G6PD	Riley	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778924	{22293322,7655862}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
1508727	326	ABCG2	rs2231142 variant (T)	\N	Decreased function	\N	\N	1508726	{25236865,21091277,22098950,18464048,18958403,15475413,15553238,10646850,11688982,11309344,25639366,26914831}	Strong	\N	421C>A is assigned a decreased function based strong evidence with numerous in vitro and clinical studies supporting decreased function. It has been found to decrease the expression of BCRP (25236865, 21091277, 22098950, 18464048, 18958403). Expression of the BCRP protein was reported to be 30–40% that of protein with the reference sequence, and expression in the placenta, specifically, was also reportedly lower (15475413, 15553238). The c.421C>A variant has been found to affect the pharmacokinetics of, response to, and toxicity of compounds that are BCRP substrates, including chemotherapeutics and endogenous compounds (10646850, 11688982, 11309344, 25639366, 26914831). Therefore, consensus among experts was decreased function with strong evidence.	{"Latino": 0.2244, "American": 0.2, "European": 0.1036, "Oceanian": 0.2047247, "East Asian": 0.3071, "Near Eastern": 0.0653, "Central/South Asian": 0.0932, "Sub-Saharan African": 0.005846004, "African American/Afro-Caribbean": 0.034866244}	f
110055	127	HLA-B	*15:02	\N	\N	\N	\N	9001	\N	\N	\N	\N	{"Latino": 0.0003047034, "American": 0.0016976056, "European": 0.000065471584, "Oceanian": 0.0079676565, "East Asian": 0.04558424, "Near Eastern": 0.00020407543, "Central/South Asian": 0.025917143, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.0009856891}	f
3685405	135	RYR1	c.1201C>G	Variant of uncertain significance	Uncertain function	\N	n/a	3685404	{35849058}	\N	\N	PM1_Sup, PM5, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
777959	340	CYP2D6	*12	\N	No function	\N	0.0	777958	{8655150,9241659,24647041,30366777}	Limited	\N	CYP2D6*12 is assigned no function based on limited evidence. CYP2D6*12 is defined by a nonsense mutation yielding a nonfunctional enzyme and was identified in a subject demonstrating markedly decreased sparteine metabolism (8655150, 9241659). Two in vitro studies found CYP2D6*12 had nondetectable enzyme activity with various substrates (24647041, 30366777). Therefore, consensus among experts was no function with an activity value of 0 based on limited evidence as it was determined the phenotypes containing this allele would be clinically distinct from phenotypes comprising normal and decreased function alleles.	{"Latino": null, "American": 0.0063913045, "European": 0.00013778963, "Oceanian": null, "East Asian": 0.0, "Near Eastern": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": 0.002101211, "African American/Afro-Caribbean": 0.00066490064}	f
779336	322	SLCO1B1	*30	\N	Uncertain function	\N	\N	779335	{22147369,33658230}	Inadequate	\N	SLCO1B1*30 is assigned uncertain function based on limited in vitro evidence and limited clinical data. One clinical study showed no statistical difference in methotrexate clearance (22147369) and one in vitro study found normal protein expression (33658230). Therefore, consensus among experts was uncertain function due to inadequate evidence.	{"American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
5294109	48	CYP2D6	*27x2	\N	Increased function	\N	2.0	777986	{18784265,18838503,24647041,30366777}	Limited	\N	CYP2D6*27x2 was deposited into PharmVar. CYP2D6*27 is assigned normal function based on limited evidence. Multiple in vitro studies found CYP2D6*27 demonstrated similar activity compared to wildtype with various substrates (18784265, 18838503). Although some in vitro studies found CYP2D6*27 demonstrated modestly decreased activity it was not convincing the magnitude of decreased activity was clinically significant (24647041, 30366777). Therefore, consensus among experts was normal function with an activity value of 1 based on limited evidence as it was determined the phenotypes containing this allele would be clinically similar to phenotypes comprising normal function alleles. Based on other normal function alleles such as *1, *2, *45, a duplication of a normal function allele is assigned an activity value of 2 and increased function.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
3685849	135	RYR1	c.12406C>A	Likely Benign	Normal function	\N	n/a	3685848	{35849058}	\N	\N	BS2_Mod	{"Latino": null, "American": null, "European": 0.0000147, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
779241	323	RYR1	c.14545G>A	Pathogenic	Malignant Hyperthermia associated	\N	n/a	779240	{33767344}	\N	\N	PS3_Mod, PS4, PM1_Sup, PP1_St	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": 0.00002414}	f
777457	344	CYP2B6	*19	Decreased function	Decreased function	\N	\N	777456	{16272958,21746968,30085944,30201214,31324697,32238417,35538637,18171905,24260284}	Limited	\N	CYP2B6*19 (c.516G>T, p.Q172H/splice defect; c.785A>G, p.K262R; c.1006C>T, p.R336C) – Decreased function: CYP2B6*19 is assigned decreased function. CYP2B6*19 contains c.516G>T which causes aberrant splicing (see CYP2B6*6 for more information). CYP2B6*19 has a unique SNP, c.1006C>T, which discriminates it from other alleles with c.516G>T. Several in vitro studies using cDNA expression systems found decreased enzyme activity for CYP2B6*19 compared to the *1 reference with various substrates (16272958, 21746968, 30201214, 30085944, 31324697, 32238417, 35538637). As is the same for *6, the mechanism for decreased activity is aberrant splicing caused by c.516G>T, which leads to reduced amounts of protein and thus, activity (14551287, 18171905, 24260284). As a result, alleles having c.516G>T are considered decreased function, regardless of the functional status of additional other variants unless these cause no function (e.g., CYP2B6*13 and CYP2B6*38). Therefore, the consensus among experts was decreased function based on the presence of c.516G>T and limited evidence.	{"Latino": null, "European": null, "Oceanian": null, "East Asian": 0.0, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": 0.016, "African American/Afro-Caribbean": 0.0}	f
777783	344	CYP2C9	*58	Decreased function	Uncertain function	\N	n/a	777782	{25142737,25075423,25884291}	Inadequate evidence	\N	CYP2C9*58 is assigned uncertain function due to inadequate evidence. CYP2C9*58 was first described in a patient requiring a low weekly warfarin dose of 9mg (25075423). No variant was observed in VKORC1 or CYP4F2 in this patient and a subsequent in silico study showed changes in hydrogen bonding which may affect the secondary structure of the protein. In vitro studies found CYP2C9*58 demonstrated decreased enzyme activity with multiple substrates (25142737, 25075423, 25884291). Consensus was not achieved among experts and therefore uncertain function was assigned.	{"Latino": 0.0, "American": null, "European": 0.0, "Oceanian": null, "East Asian": null, "Near Eastern": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778382	327	DPYD	c.1180C>T	Normal function	Normal function	\N	1.0	778381	{24648345}	Limited	\N	5-fluorouracil (in vitro)	{"Latino": 0.00010, "European": 0.0, "East Asian": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778416	325	DPYD	c.1615G>A	Normal function	Normal function	\N	1.0	778415	{24648345}	Limited	\N	5-fluorouracil (in vitro)	{"Latino": 0.0, "European": 0.000013374884, "East Asian": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": 0.0041011903, "African American/Afro-Caribbean": 0.0031082802}	f
3685971	135	RYR1	c.14818G>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685970	{35849058}	\N	\N	PS4_Mod, PM1_Sup, PP3_Mod	{"Latino": null, "American": null, "European": 0.00001471, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685977	135	RYR1	c.14918C>T	Likely Pathogenic	Malignant Hyperthermia associated	\N	n/a	3685976	{33767344}	\N	\N	PS4_Mod, PM1_Sup, PP3_Mod, PP1_Sup	{"Latino": null, "American": null, "European": 0.0000441, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": 0.00002414}	f
3685981	135	RYR1	c.15059G>C	Variant of uncertain significance	Uncertain function	\N	n/a	3685980	{35849058}	\N	\N	PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
777575	344	CYP2C19	*24	\N	No function	\N	\N	777574	{25001882,27578295,31713493}	Limited	\N	CYP2C19*24 is assigned no function based on limited evidence. In vitro studies found CYP2C19*24 demonstrated nondetectable enzyme activity compared to wildtype with mephenytoin, clopidogrel, and omeprazole substrates (25001882, 27578295, 31713493). Additionally, CYP2C19*24 had less holoprotein compared to wildtype suggesting the protein is less stable resulting in little to no enzyme activity (27578295). Therefore, consensus among experts was no function based on limited evidence as it was determined the phenotypes containing this allele would be clinically distinct from phenotypes comprising normal function and decreased function alleles.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": 0.00018712576, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
777793	326	CYP2C9	*63	Uncertain function	Uncertain function	\N	n/a	777792	{33536773}	Inadequate evidence	\N	CYP2C9*63 is assigned uncertain funciton due to inadequate evidence. The nonsynonymous variants present in CYP2C9*63 is predicted to be deleterious in both SIFT and Polyphen predictions. There are no in vitro or clinical studies reported. Consensus was not achieved among experts and therefore uncertain function was assigned.	{"Latino": 0.0, "American": null, "European": 0.0, "Oceanian": null, "East Asian": null, "Near Eastern": 0.0, "Central/South Asian": 0.00050, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
3685361	135	RYR1	c.529C>T	Pathogenic	Malignant Hyperthermia associated	\N	n/a	3685360	{35849058}	\N	\N	PS2_PM6_Mod, PS4, PM1, PP1_St, PP3_Mod, BS2_Mod	{"Latino": null, "American": null, "European": 0.0000147, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685371	135	RYR1	c.652G>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685370	{35849058}	\N	\N	PS4_Sup, PM1	{"Latino": null, "American": null, "European": 0.0000147, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
779159	323	RYR1	c.742G>C	Pathogenic	Malignant Hyperthermia associated	\N	n/a	779158	{33767344}	\N	\N	PS1, PS3_Mod, PS4_Mod, PM1_Sup, PP1_Mod, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": 0.0001922, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
777995	340	CYP2D6	*31	\N	No function	\N	0.0	777994	{15726636,20473659,24647041,30366777}	Moderate	\N	CYP2D6*31 is assigned no function based on moderate evidence in heterozygous subjects and in vitro studies. CYP2D6*31 was first identified in a subject with CYP2D6 *4/*31 genotype demonstrating markedly decreased metoprolol metabolism with an AUC more than three times greater than the AUC of wildtype subjects and similar AUC to subjects with two known nonfunctional alleles (15726636). CYP2D6*31 was described in another subject demonstrating decreased dextromethorphan metabolism based on urine metabolites (20473659). Multiple in vitro studies found CYP2D6*31 had nondetectable or markedly decreased enzyme activity compared to wildtype with various substrates (15726636, 24647041, 30366777). CYP2D6*31 is defined by three amino acid substitutions and an analysis of the crystal structure and docking study suggested the Arg440His substitution causes reduced reductase binding resulting in impaired enzyme activity (15726636). Therefore, consensus among experts was no function with an activity value of 0 based on moderate evidence.	{"Latino": 0.007475, "American": 0.006, "European": 0.001476514, "Oceanian": 0.0, "East Asian": 0.0, "Near Eastern": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.0}	f
778791	296	G6PD	Miaoli	II/Deficient	II/Deficient	\N	\N	778790	{22293322,9444913}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
779183	323	RYR1	c.1840C>T	Pathogenic	Malignant Hyperthermia associated	\N	n/a	779182	{33767344}	\N	\N	PS3_Mod, PS4, PM5, PP1_St, PP3_Mod, BS2_Mod	{"Latino": null, "American": null, "European": 0.00020354411, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": 0.00002416}	f
779185	323	RYR1	c.1841G>T	Pathogenic	Malignant Hyperthermia associated	\N	n/a	779184	{33767344}	\N	\N	PS3_Mod, PS4, PP1_St, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685457	135	RYR1	c.2447C>T	Likely Benign	Normal function	\N	n/a	3685456	{35849058}	\N	\N	PS4_Sup, BS2_Mod, BS3_Sup	{"Latino": null, "American": null, "European": 0.0000147, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": 0.00002411}	f
3685373	135	RYR1	c.677T>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685372	{35849058}	\N	\N	PS4_Mod, PM1	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
6481195	6	NAT2	*5	Slow	Decreased function	\N	\N	6481194	{9154882,8781741,28653770,8102597,30564082,15558239,7668286,1451720,10744128,22092036,1872889,8689813,20040334,17011540,22970273,16531626,15565348,9321764,9110365,31257615,29018032,24702251,24444407,15110095,27509179,11773863,20801937,16003747,21750470,9565293,9891107,24221535,8287065,27223070,8001235,8923605,10762005,8081359,35928262,28752039,17505821,21946899,16570187,15032315,18167504,17434923,33815485,18680467,19336229,15564878,7669073,11337936}	Definitive	\N	NAT2*5 is assigned decreased function based on definitive evidence. The NAT gene nomenclature committee has historically assigned acetylation activity to alleles as either "rapid" or "slow", classifying the NAT2*5 allele as "slow" . Under the CPIC allele function terminology, slow acetylation alleles are categorized as "Decreased Function". The functional SNV c.341T>C (p.I114T) in NAT2*5 has been studied for more than 25 years and has shown decreased N-acetylation activity in numerous clinical and in vitro studies using various substrates. Clinical studies have demonstrated that individuals homozygous for NAT2*5 or heterozygous for NAT2*5 in combination with another decreased function allele exhibit decreased acetylation activity toward caffeine metabolites (8102597, 7668286, 10744128, 9891107, 20801937, 22970273, 24221535, 28653770), isoniazid (9154882, 9321764, 19336229, 35928262) sulfonamides (1872889, 15032315, 16570187, 18167504, 21946899), and dapsone (10762005). Individuals homozygous for NAT2*5 or heterozygous for NAT2*5 in combination with another decreased function allele exhibit increased hydralazine exposure (24702251, 31257615). Five out of nine variant effect predictors tested by CPIC staff predict that c.341T>C (p.I114T) impairs protein function. In vitro studies show that NAT2*5 exhibits similar thermostability to NAT2*4, which was previously used as the reference allele (8081359, 15564878, 17434923, 11337936), however NAT2*5 is subjected to enhanced protein degradation by the proteasome (15564878), indicating decreased protein levels as the molecular mechanism for the decreased acetylation activity observed.	\N	f
6481201	6	NAT2	*10	\N	Uncertain function	\N	\N	6481200	{17434923,18680467}	Inadequate	\N	NAT2*10 is assigned uncertain function based on inadequate evidence. The NAT gene nomenclature committee has historically assigned acetylation activity to alleles as either "rapid" or "slow", classifying the NAT2*10 allele as "slow" and possibly substrate dependent. Under the CPIC allele function terminology, slow acetylation alleles are categorized as "Decreased Function". NAT2*10 is characterized by the core SNVs c.499G>A (p.E167K) and c.803G>A (p.R268K). c.803G>A defines NAT2*4, formerly considered the reference allele, which has repeatedly exhibited increased function in vivo and in vitro. c.499G>A; p.E167K was shown to decrease N-acetylation activity toward sulfamethazine in vitro due to decreased protein levels (17434923). Published in silico modeling predicts that c.499G>A (p.E167K) decreases hydrogen bond capacity, decreases hydrophobicity, and alters protein charge (18680467). However, eight out of nine variant effect predictors tested by CPIC staff predict that c.499G>A is neutral/tolerated for protein function. The lack of in vivo evidence, along with the conflicting in vitro and computational evidence, results in the assignment of uncertain function.	\N	f
779286	323	SLCO1B1	*5	\N	No function	\N	\N	779285	{11477075,32961594,21245207}	Definitive	\N	SLCO1B1*5 is assigned no function based on definitive evidence in heterozygous and SLCO1B1*5/*15 compound heterozygote individuals. The plasma levels of highly sensitive OATP1B1 endogenous substrates GCDCA-3G and GDCA-3G are significantly higher in SLCO1B1*1/*5 and SLCO1B1*5/*15 heterozygotes than in individuals with the SLCO1B1*1/*1 homozygotes (32961594). In vitro studies have demonstrated significantly reduced uptake of estrone sulfate and estradiol 17beta-d-glucuronide (11477075), and several other substrates compared to SLCO1B1*1 (21245207).Therefore, consensus among experts was no function on definitive evidence.	{"American": 0.0, "European": 0.02040433, "Oceanian": 0.0, "East Asian": 0.0010003184, "Near Eastern": 0.05, "Central/South Asian": 0.004471154, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.0}	f
777719	344	CYP2C9	*26	Decreased function	Decreased function	\N	0.5	777718	{23752738,19541829,16788382}	Limited	\N	CYP2C9*26 is assigned decreased function based on limited evidence. Multiple in vitro studies found CYP2C9*26 demonstrated decreased clearance compared to wildtype. These studies used different cell systems and substrates included warfarin, tolbutamide, diclofenac, losartan, and glimepiride (23752738, 19541829, 16788382). Therefore, consensus among experts was decreased function with an activity value of 0.5 based on limited evidence as it was determined the phenotypes containing this allele would be clinically distinct from phenotypes comprising normal function alleles.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": 0.002, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778037	340	CYP2D6	*52	\N	Decreased function	\N	0.25	778036	{24647041,19364831,23897164,30366777}	Limited	\N	CYP2D6*52 is assigned decreased function with an activity value of 0.25 based on limited evidence. Studies found CYP2D6*52 demonstrated decreased enzyme activity compared to wildtype with tamoxifen, bufuralol, dextromethorphan, and primaquine substrates (19364831, 23897164, 24647041, 30366777). This allele has 100C>T (the *10 SNP), 3854G>A (E410K) which we believe does not change function and 4181G>C (*2 SNP) which we also believe is benign. Therefore, consensus among experts was decreased function with limited evidence.	{"Latino": null, "American": 0.0, "European": 0.0, "Oceanian": null, "East Asian": 0.0016893354, "Near Eastern": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": 0.0012988754, "African American/Afro-Caribbean": 0.0}	f
778793	296	G6PD	Shinshu	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778792	{22293322,8193373}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
3685531	135	RYR1	c.6302T>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685530	{35849058}	\N	\N	PM1, BP4	{"Latino": null, "American": null, "European": 0.0000147, "East Asian": null, "Near Eastern": 0.004228129, "Central/South Asian": null, "Sub-Saharan African": 0.00002413}	f
779187	323	RYR1	c.6487C>T	Pathogenic	Malignant Hyperthermia associated	\N	n/a	779186	{33767344}	\N	\N	PS3_Mod, PS4_Mod, PM1_Sup, PM5, PP1_St, PP3_Mod, BS2_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
779191	323	RYR1	c.6502G>A	Pathogenic	Malignant Hyperthermia associated	\N	n/a	779190	{33767344}	\N	\N	PS3_Mod, PS4, PM1, PP1_St, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685569	135	RYR1	c.6635T>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685568	{35849058}	\N	\N	PM1, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
777721	344	CYP2C9	*27	Uncertain function	Uncertain function	\N	n/a	777720	{23752738,16788382,23844998,24118918,25142737,25144335,25951663,25476996,25614704,25832633,25884291,25924705,27163851,24077631}	Inadequate evidence	\N	CYP2C9*27 is assigned uncertain function due to inadequate evidence. One subject with CYP2C9 *1/*27 genotype exhibited similar clearance compared to wildtype subjects based on tolbutamide plasma concentrations after one 500mg dose (25614704). In vitro studies showed conflicting results with CYP2C9*27 exhibiting enzyme activity ranging from decreased to increased compared to wildtype with various substrates (24118918, 23844998, 25476996, 25832633, 24077631, 25144335, 25951663, 23752738, 16788382, 25884291, 25614704, 25924705, 27163851, 25142737). Consensus was not achieved among experts and therefore uncertain function was assigned.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": 0.0016176943, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": 0.0}	f
778007	340	CYP2D6	*37	\N	Uncertain function	\N	n/a	778006	{24647041,30366777}	Inadequate	\N	CYP2D6*37 is assigned uncertain function based on inadequate evidence. In vitro studies found CYP2D6*37 demonstrated decreased enzyme activity compared to wildtype with tamoxifen, bufuralol, dextromethorphan, and primaquine substrates (24647041, 30366777). Consensus was not achieved among experts as data were sparse and not consistent among substrates. Therefore, uncertain function was assigned.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": 0.0, "Near Eastern": 0.0, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778039	340	CYP2D6	*53	\N	Normal function	\N	1.0	778038	{18784265,24647041,30366777}	Limited	\N	CYP2D6*53 is assigned normal function based on limited evidence. Multiple in vitro studies found CYP2D6*53 had similar enzyme activity compared to wildtype with multiple substrates (18784265, 24647041). Although one in vitro study found CYP2D6*53 demonstrated decreased clearance compared to wildtype with a primaquine substrate (30366777) the experts did not find this result convincing as CYP2D6*53 demonstrated similar activity compared to wildtype towards a majority of substrates. Therefore, consensus among experts was normal function with an activity value of 1 based on limited evidence.	{"Latino": 0.005, "American": null, "European": null, "Oceanian": null, "East Asian": 0.00019958949, "Near Eastern": 0.0, "Central/South Asian": null, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": null}	f
778356	331	DPYD	c.632A>G	No function	No function	\N	0.0	778355	{24648345}	Limited	\N	5-fluorouracil (in vitro)	{"Latino": 0.0, "European": 0.000013646893, "East Asian": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
3685627	135	RYR1	c.7097C>G	Variant of uncertain significance	Uncertain function	\N	n/a	3685626	{35849058}	\N	\N	PS4_Sup, PM1, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685667	135	RYR1	c.7358T>C	Likely Pathogenic	Malignant Hyperthermia associated	\N	n/a	3685666	{35849058}	\N	\N	PS2_PM6_Mod, PS4_Sup, PM1, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
6355308	9	CFTR	L997F(G>C)	\N	ivacaftor responsive	\N	\N	6355307	{}	\N	\N	\N	\N	f
6355310	9	CFTR	L997F(G>T)	\N	ivacaftor responsive	\N	\N	6355309	{}	\N	\N	\N	\N	f
6355314	9	CFTR	M152V	\N	ivacaftor responsive	\N	\N	6355313	{}	\N	\N	\N	\N	f
6355316	9	CFTR	M952I(G>A)	\N	ivacaftor responsive	\N	\N	6355315	{}	\N	\N	\N	\N	f
6355318	9	CFTR	M952I(G>C)	\N	ivacaftor responsive	\N	\N	6355317	{}	\N	\N	\N	\N	f
6355320	9	CFTR	M952I(G>T)	\N	ivacaftor responsive	\N	\N	6355319	{}	\N	\N	\N	\N	f
777473	344	CYP2B6	*27	\N	Uncertain function	\N	\N	777472	{17235330,21746968,30201214}	Inadequate	\N	CYP2B6*27 (c.593T>C, p.M198T) – Uncertain function: CYP2B6*27 is assigned uncertain function. Three in vitro studies using cDNA expression systems found that CYP2B6*27 demonstrated decreased enzyme activity compared to the *1 reference for most substrates, although increased activity was seen for one non-drug probe substrate (21746968, 17235330, 30201214). This discrepancy is probably due to differences in the in vitro expression systems and substrates used. One subject with the CYP2B6*6/*27 genotype had an elevated efavirenz AUC compared to the *1 reference (17235330). Consensus was not achieved among experts due to insufficient evidence of this variant in human subjects. Therefore, uncertain function was assigned based on inadequate evidence.	{"Latino": 0.0, "European": 0.0, "Oceanian": null, "East Asian": 0.008, "Near Eastern": null, "Central/South Asian": 0.0, "Sub-Saharan African": 0.006, "African American/Afro-Caribbean": null}	f
778029	340	CYP2D6	*48	\N	Normal function	\N	1.0	778028	{18784265,24647041,30366777}	Limited	\N	CYP2D6*48 is assigned normal function based on limited evidence. Multiple in vitro studies found CYP2D6*48 had similar enzyme activity compared to wildtype with multiple substrates (18784265, 24647041, 30366777). Therefore, consensus among experts was normal function with an activity value of 1 based on limited evidence.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": 0.00024301164, "Near Eastern": 0.0, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
6609707	1	CFTR	F508C,S1251N	\N	ivacaftor responsive	\N	\N	6606011	{}	\N	\N	\N	\N	f
6355312	9	CFTR	L1480P	\N	ivacaftor responsive	\N	\N	6355311	{}	\N	\N	\N	\N	f
6355322	9	CFTR	M952T	\N	ivacaftor responsive	\N	\N	6355321	{}	\N	\N	\N	\N	f
6355332	9	CFTR	Q1291R	\N	ivacaftor responsive	\N	\N	6355331	{}	\N	\N	\N	\N	f
6355326	9	CFTR	Q237E	\N	ivacaftor responsive	\N	\N	6355325	{}	\N	\N	\N	\N	f
6355328	9	CFTR	Q237H	\N	ivacaftor responsive	\N	\N	6355327	{}	\N	\N	\N	\N	f
6355330	9	CFTR	Q359R	\N	ivacaftor responsive	\N	\N	6355329	{}	\N	\N	\N	\N	f
6355340	9	CFTR	R117G	\N	ivacaftor responsive	\N	\N	6355339	{}	\N	\N	\N	\N	f
6355344	9	CFTR	R117L	\N	ivacaftor responsive	\N	\N	6355343	{}	\N	\N	\N	\N	f
6355346	9	CFTR	R117P	\N	ivacaftor responsive	\N	\N	6355345	{}	\N	\N	\N	\N	f
6355348	9	CFTR	R170H	\N	ivacaftor responsive	\N	\N	6355347	{}	\N	\N	\N	\N	f
6355352	9	CFTR	R347L	\N	ivacaftor responsive	\N	\N	6355351	{}	\N	\N	\N	\N	f
6355336	9	CFTR	R75Q	\N	ivacaftor responsive	\N	\N	6355335	{}	\N	\N	\N	\N	f
778384	327	DPYD	c.1181G>T	Normal function	Normal function	\N	1.0	778383	{24648345}	Limited	\N	5-fluorouracil (in vitro)	{"Latino": 0.0, "European": 0.0000132841415, "East Asian": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": 0.0008968254, "African American/Afro-Caribbean": 0.0}	f
2899145	133	CYP2B6	*40	Decreased function	Decreased function	\N	\N	2899144	{14551287,18171905,24260284,38596098}	Limited	\N	CYP2B6*40 (c.516G>T, p.Q172H/splice defect; c.785A>G, p.K262R; c.1133G>A, p.R378Q) – Decreased function: CYP2B6*40 is assigned decreased function. CYP2B6*40 contains c.516G>T which causes aberrant splicing (see CYP2B6*6 for more information). As is the same for *6, the mechanism for decreased activity is aberrant splicing caused by c.516G>T, which leads to reduced amounts of protein and thus, activity (14551287, 18171905, 24260284). As a result, alleles having c.516G>T are considered decreased function, regardless of the functional status of additional other variants unless these cause no function (e.g., CYP2B6*13 and CYP2B6*38). A single in vitro study reported decreased function for p.R378Q using buproprion and efavirez as probes (38596098). Therefore, the consensus among experts was decreased function based on the presence of c.516G>T and limited evidence.	{"Latino": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
2677054	105	CYP2D6	*171	\N	\N	\N	\N	2677053	\N	\N	\N	\N	\N	f
777471	344	CYP2B6	*26	Decreased function	Decreased function	\N	\N	777470	{17918089,30085944,30201214,32238417,34100292,18171905,24260284}	Limited	\N	CYP2B6*26 (c.499C>G, p.P167A; c.516G>T, p.Q172H/splice defect; c.785A>G, p.K262R) – Decreased function: CYP2B6*26 is assigned decreased function. CYP2B6*26 contains c.516G>T which causes aberrant splicing (see CYP2B6*6 for more information). One study evaluating efavirenz plasma concentrations among patients with HIV found CYP2B6*26 was associated with elevated efavirenz concentrations compared to the *1 reference and has similar function to CYP2B6*6. This was demonstrated by similar efavirenz concentrations among CYP2B6 *6/*26 subjects CYP2B6 *6/*6 subjects (17918089). Although one in vitro study using a cDNA expression system found that CYP2B6*26 demonstrated increased enzyme activity compared to the *1 reference (30201214), the experts did not find these results convincing as it has previously been shown that in vitro expression systems may not adequately reflect CYP2B6*6 expression and function, and therefore also not be a suitable system to assess CYP2B6*26. As is the same for *6, the mechanism for decreased activity is aberrant splicing caused by c.516G>T, which leads to reduced amounts of protein and thus, activity (14551287, 18171905, 24260284). As a result, alleles having c.516G>T are considered decreased function, regardless of the functional status of additional other variants unless these cause no function (e.g., CYP2B6*13 and CYP2B6*38). Therefore, the consensus among experts was decreased function based on the presence of c.516G>T and limited evidence.	{"Latino": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
777477	344	CYP2B6	*29	Decreased function	Decreased function	\N	\N	777476	{17885627,28181240}	Limited	\N	CYP2B6*29 (CYP2B7-CYP2B6 hybrid gene) – Decreased function: CYP2B6*29 is assigned decreased function. This allele is a hybrid consisting of CYP2B7 (exons 1-4) and CYP2B6 (exons 5-9) harboring 23 amino acid changes compared to the protein encoded by the CYP2B6*1 reference. Among those is c.516G>T which is one of the function-altering variants defining CYP2B6*6. CYP2B6*29 was identified in a subject with an elevated efavirenz AUC compared to the *1 reference and similar to those seen in patients carrying one decreased function allele (17885627). One in vitro study found that primary human hepatocytes of subjects with a CYP2B6*29 allele had slightly lower protein expression and enzyme activity compared to the *1 reference (28181240). The same study also showed that the AUC for 4-OH-cyclophosphamide was significantly lower for patients with a CYP2B6*1/*29 genotype compared to *1/*1 (28181240). Therefore, consensus among experts was decreased function based on limited evidence.	{"Latino": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
2899163	133	CYP2B6	*49	\N	Uncertain function	\N	\N	2899162	{38596098}	Inadequate	\N	CYP2B6*49 (c.1301G>A, p.R434Q) – Uncertain function: CYP2B6*49 is assigned uncertain function due to inadequate evidence describing function. A single in vitro study reported decreased function for p.R434Q using buproprion and efavirez as probes (38596098).	{"Latino": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
3685721	135	RYR1	c.8290G>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685720	{35849058}	\N	\N	None	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685729	135	RYR1	c.8527T>C	Variant of uncertain significance	Uncertain function	\N	n/a	3685728	{35849058}	\N	\N	PS4_Sup	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
778171	339	CYP2D6	*126	\N	Unknown function	\N	n/a	778170	{}	No Evidence	\N	CYP2D6*126 is assigned unknown function due to no literature describing function of this allele. Therefore, consensus among experts was unknown function due to no available evidence.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
777491	344	CYP2B6	*36	Decreased function	Decreased function	\N	\N	777490	{23418033,18171905,24260284}	Limited	\N	CYP2B6*36 (c.-82T>C, c.516G>T, p.Q172H/splice defect; c.785A>G, p.K262R) – Decreased function: CYB2B6*36 is assigned decreased function. CYP2B6*36 contains c.516G>T which causes aberrant splicing (see CYP2B6*6 for more information) (23418033). As is the same for *6, the mechanism for decreased activity is aberrant splicing caused by c.516G>T, which leads to reduced amounts of protein and thus, activity (14551287, 18171905, 24260284). As a result, alleles having c.516G>T are considered decreased function, regardless of the functional status of additional other variants unless these cause no function (e.g., CYP2B6*13 and CYP2B6*38). Therefore, the consensus among experts was decreased function based on the presence of c.516G>T and limited evidence.	{"Latino": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
777581	344	CYP2C19	*28	\N	Normal function	\N	\N	777580	{25001882,20712527}	Limited	\N	CYP2C19*28 is assigned normal function based on limited in vitro and computational evidence. An in vitro study found CYP2C19*28 had similar intrinsic clearance compared to wildtype with a mephenytoin substrate (25001882). A computational analysis including splice site, mFold and nonsynonymous mutation analysis, did not find a deleterious impact on enzyme function (20712527). Although CYP2C19*28 was found to have increased intrinsic clearance compared to wildtype with a clopidogrel substrate in vitro (25001882), the experts did not find this result convincing as computational analysis and in vitro data with mephenytoin did not support increased function. Therefore, consensus among experts was normal function based on limited evidence as it was determined the phenotypes containing this allele would be clinically similar to phenotypes comprising normal function alleles.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": 0.0, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": 0.0037037036, "African American/Afro-Caribbean": null}	f
777597	344	CYP2C19	*36	\N	No function	\N	\N	777596	{31260137}	Limited	\N	CYP2C19*36 is assigned no function based on limited evidence. CYP2C19*36 is a complete deletion of the CYP2C19 gene and was identified by interrogation of multiple databases of clinical chromosomal microarray data (31260137). Therefore, because a gene deletion would not result in protein formation, consensus among experts was no function based on limited evidence as it was determined the phenotypes containing this allele would be clinically distinct from phenotypes comprising normal function and decreased function alleles.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
3685695	135	RYR1	c.7771C>T	Variant of uncertain significance	Uncertain function	\N	n/a	3685694	{35849058}	\N	\N	None	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685699	135	RYR1	c.7778G>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685698	{35849058}	\N	\N	PS4_Sup	{"Latino": null, "American": null, "European": 0.00004422, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
777731	344	CYP2C9	*32	Uncertain function	Uncertain function	\N	n/a	777730	{23752738}	Inadequate evidence	\N	CYP2C9*32 is assigned uncertain function due to inadequate evidence. In one in vitro study, CYP2C9*32 demonstrated similar enzyme activity compared to wildtype with a warfarin and tolbutamide substrate (23752738). Therefore, consensus among experts was uncertain function due to insufficient evidence.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
3685709	135	RYR1	c.8005G>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685708	{35849058}	\N	\N	None	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
777579	344	CYP2C19	*26	\N	Decreased function	\N	\N	777578	{19661214,25001882}	Limited	\N	CYP2C19*26 is assigned decreased function based on limited evidence in a heterozygous subject and in vitro studies. CYP2C19*26 was first described in a subject also carrying the CYP2C19*2 allele and demonstrated decreased omeprazole metabolism compared to wildtype and CYP2C19 *1/*2 or CYP2C19*1/*3 subjects based on the plasma metabolite ratio. This result was correlated with an in vitro study which showed CYP2C19*26 demonstrated decreased intrinsic clearance compared to wildtype with mephenytoin and omeprazole substrates (19661214). An additional in vitro study using a different cell system similarly found CYP2C19*26 demonstrated decreased intrinsic clearance compared to wildtype with mephenytoin and clopidogrel substrates (25001882). Therefore, consensus among experts was decreased function based on limited evidence as it was determined the phenotypes containing this allele would be clinically distinct from phenotypes comprising normal function alleles.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": 0.0, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778446	325	DPYD	c.2161G>A	Normal function	Normal function	\N	1.0	778445	{24648345}	Limited	\N	5-fluorouracil (in vitro)	{"Latino": 0.00023592282, "European": 0.0001946586, "East Asian": 0.0, "Central/South Asian": 0.000089406414, "Sub-Saharan African": 0.0009821429, "African American/Afro-Caribbean": 0.0}	f
778735	296	G6PD	Hammersmith	III/Deficient	III/Deficient	\N	\N	778734	{22293322,12064901,10192449}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
779017	296	G6PD	Kamiube, Keelung	III/Deficient	III/Deficient	\N	\N	779016	{22293322,511159,9192788,9444913}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
778849	296	G6PD	La Jolla	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778848	{22293322,12064902}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
778769	296	G6PD	Liuzhou	II/Deficient	II/Deficient	\N	\N	778768	{22293322,17018380}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
779221	323	RYR1	c.7373G>A	Pathogenic	Malignant Hyperthermia associated	\N	n/a	779220	{33767344}	\N	\N	PS3_Mod, PS4, PM1, PP1_St, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685677	135	RYR1	c.7373G>T	Likely Pathogenic	Malignant Hyperthermia associated	\N	n/a	3685676	{35849058}	\N	\N	PS4_Mod, PM1_Sup, PM5, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
779223	323	RYR1	c.7522C>T	Likely Pathogenic	Malignant Hyperthermia associated	\N	n/a	779222	{33767344}	\N	\N	PS3_St, PS4_Mod, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
777475	344	CYP2B6	*28	No function	No function	\N	\N	777474	{17235330,20517174,30201214}	Limited	\N	CYP2B6*28 (c.917C>G, p.T306S; c.1132C>T, p.R378X) – No function: CYP2B6*28 is assigned no function. CYP2B6*28 is defined by a nonsense mutation which results in a premature stop codon resulting in a truncated protein. One study evaluating efavirenz plasma concentrations in patients with HIV found a subject with CYP2B6 *6/*28 genotype had elevated efavirenz AUC compared to the *1 reference and CYP2B6 *6/*6 subjects (17235330). In vitro studies using cDNA expression systems found that CYP2B6*28 demonstrated no enzyme activity (17235330, 20517174). Therefore, consensus among experts was no function based on limited evidence.	{"Latino": 0.0, "European": 0.0, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": 0.006, "African American/Afro-Caribbean": null}	f
777489	344	CYP2B6	*35	\N	Uncertain function	\N	\N	777488	{23418033,30201214}	Inadequate	\N	CYP2B6*35 (c.-82T>C; c.329G>T, p.G110V; c.341T>C, p.I114T; c.444G>T, p.E148D; c.593T>C, p.M198T; c.835G>C, p.A279P) – Uncertain function: CYB2B6*35 is assigned uncertain function. Two in vitro studies using cDNA expression systems provided inconclusive evidence for CYP2B6*35 function (23418033, 30201214). Therefore, consensus among experts was uncertain function based on inadequate evidence.	{"Latino": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
777689	344	CYP2C9	*11	Decreased function	Decreased function	\N	0.5	777688	{15284535,23752738,15289788,15970795,25951663,16220110,21811894,23844998,24118918,25142737,25144335,25476996,25832633,25884291,25924705,27163851,27199745,24077631}	Definitive	\N	CYP2C9*11 is assigned decreased function based on definitive evidence in heterozygous patients and in vitro studies. Four subjects carrying the CYP2C9*11 allele (n=3 CYP2C9*1/*11, n=1 CYP2C9*8/*11) demonstrated decreased phenytoin metabolism compared to wildtype subjects based on urinary excretion of a phenytoin metabolite after a single 300mg dose (16220110). Three CYP2C9*1/*11 patients on a stable dose of warfarin required a 33% lower warfarin dose compared to CYP2C9*1/*1 patients which correlated with the in vitro investigation where CYP2C9*11 had low levels of enzyme expression, decreased half-life, and 70% catalytic efficiency compared to wildtype; these results are suggestive of improper protein folding leading to decreased stability and reduced enzyme activity (15970795). An examination of the crystal structure showed the substitution which defines the CYP2C9*11 allele disrupts the sole extrahelical hydrogen bonding interaction, destabilizing the structure (15284535). In vitro studies showed CYP2C9*11 demonstrated decreased metabolism of tolbutamide, warfarin, glimepiride, carvedilol, fluoxetine, flurbiprofen, mestranol, diclofenac, and losartan compared to wildtype (15284535, 23752738, 24118918, 25476996, 25884291, 27199745, 25144335, 25924705, 25951663, 23844998). Although other in vitro studies showed CYP2C9*11 had similar activity compared to wildtype, the experts did not find these results convincing as in these studies CYP2C9*2 and/or CYP2C9*3 which definitively have decreased function and no function, respectively, also demonstrated similar activity compared to wildtype in these studies (25142737, 25832633, 27163851). The experts did not find the result of an in vitro study which showed CYP2C9*11 had similar activity compared to wildtype with a tolbutamide substrate (24077631) convincing because this result was not replicated as two separate in vitro studies which used two different systems and showed CYP2C9*11 demonstrated decreased clearance compared to wildtype, as described previously (15284535, 23752738). The experts also did not deem the results of a study which found no difference in losartan metabolism among four subjects carrying the CYP2C9*11 allele nor a study which found no difference in acenocoumarol metabolism among one subject with CYP2C9*1/*11 genotype as convincing conflicting evidence due to the small sample size (15289788, 21811894). Therefore, consensus among experts was decreased function with an activity value of 0.5 based on definitive evidence.	{"Latino": 0.002901849, "American": 0.0028040742, "European": 0.0016443896, "Oceanian": null, "East Asian": 0.00029316536, "Near Eastern": 0.0, "Central/South Asian": 0.0010429447, "Sub-Saharan African": 0.025685642, "African American/Afro-Caribbean": 0.013860963}	f
778061	340	CYP2D6	*64	\N	Uncertain function	\N	n/a	778060	{24647041,30366777}	Inadequate	\N	CYP2D6*64 is assigned uncertain function due to inadequate evidence. In vitro studies found CYP2D6*64 demonstrated decreased enzyme activity compared to wildtype with various substrates (24647041, 30366777). Consensus was not achieved among experts as data were sparse. Therefore, uncertain function was assigned.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": 0.0, "Near Eastern": 0.0, "Central/South Asian": null, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": null}	f
779031	296	G6PD	Fukaya	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	779030	{22293322,1945893}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
778777	296	G6PD	Mahidol	III/Deficient	III/Deficient	\N	\N	778776	{22293322,2503817}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": 0.0, "European": 0.0, "East Asian": 0.00007218132, "Central/South Asian": 0.000366934, "African American/Afro-Caribbean": 0.0}	f
778809	296	G6PD	Nilgiri	II/Deficient	II/Deficient	\N	\N	778808	{22293322,18043863}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
777593	344	CYP2C19	*34	\N	Uncertain function	\N	\N	777592	{23799451}	Inadequate	\N	CYP2C19*34 is assigned uncertain function due to inadequate evidence. CYP2C19*34 was identified in a patient heterozygous for the CYP2C19*2 allele who experienced adverse effects with venlafaxine and a supratherapeutic nortriptyline level. CYP2C19 enzyme function was not adequately assessed as CYP2D6 is involved in metabolism of antidepressants such as nortriptyline and this patient was a CYP2D6 intermediate metabolizer (23799451). Therefore, consensus among experts was uncertain function due to inadequate evidence.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": 0.0, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
777703	344	CYP2C9	*18	Uncertain function	Uncertain function	\N	n/a	777702	{23752738,16099926}	Inadequate evidence	\N	CYP2C9*18 is assigned uncertain function due to inadequate evidence. In one in vitro study, CYP2C9*18 protein expression could not be detected in an E.coli system (16099926). CYP2C9*18 protein expression was detected in a separate study using COS-7 cells and no enzyme activity was detected with warfarin and tolbutamide substrates (23752738). Therefore, consensus among experts was uncertain function due to insufficient evidence.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
777775	344	CYP2C9	*54	Uncertain function	Uncertain function	\N	n/a	777774	{24077631,24118918,25142737,25144335,25476996,25832633,25884291,25951663,25924705,27163851,23844998}	Inadequate evidence	\N	CYP2C9*54 is assigned uncertain function due to inadequate evidence. In vitro studies found CYP2C9*54 demonstrated enzyme activity ranging from decreased to increased compared to wildtype with various substrates (24077631, 24118918, 25142737, 25144335, 25476996, 25832633, 25951663, 25884291, 25924705, 27163851, 23844998). Therefore, consensus among experts was uncertain function due to inadequate evidence.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778687	296	G6PD	Aures	III/Deficient	III/Deficient	\N	\N	778686	{22293322,33413378,22963789,23006493,8860007,7959686,18226470,8490627}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": 0.0, "European": 0.0, "East Asian": 0.00014428973, "Central/South Asian": 0.0, "African American/Afro-Caribbean": 0.0}	f
6235064	8	CYP2C19	*40	\N	\N	\N	\N	6235063	\N	\N	\N	\N	\N	f
6235066	8	CYP2C19	*41	\N	\N	\N	\N	6235065	\N	\N	\N	\N	\N	f
778450	325	DPYD	c.2194G>A (*6)	Normal function	Normal function	\N	1.0	778449	{23328581}	Moderate	\N	5-fluorouracil (in vitro)	{"Latino": 0.027319003, "European": 0.044963934, "East Asian": 0.018249057, "Central/South Asian": 0.09505568, "Sub-Saharan African": 0.02695635, "African American/Afro-Caribbean": 0.016}	f
778935	296	G6PD	Iowa, Walter Reed, Springfield	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778934	{22293322,2602358}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
777733	344	CYP2C9	*33	Decreased function	No function	\N	0.0	777732	{23752738,18971529,23844998,24118918,25142737,25951663,25144335,25476996,25832633,25884291,27163851,19541829,24077631}	Limited	\N	CYP2C9*33 is assigned no function based on limited evidence. Multiple in vitro studies using different cell systems found CYP2C9*33 demonstrated decreased clearance for numerous substrates compared to wildtype and similar clearance compared to CYP2C9*3 which definitively has no function (23752738, 18971529, 23844998, 24118918, 25142737, 25951663, 25144335, 25476996, 25832633, 25884291, 27163851, 19541829, 24077631). Although one patient with CYP2C9 *1/*33 genotype had their blood pressure lowered with losartan, the experts did not find this result convincing due to the small sample size (18971529). Therefore, consensus among experts was no function with an activity value of 0 based on limited evidence as it was determined the phenotypes containing this allele would be clinically distinct from phenotypes comprising normal and decreased function alleles.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": 0.00065227173, "Near Eastern": 0.001, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
777795	326	CYP2C9	*64	Uncertain function	Uncertain function	\N	n/a	777794	{33536773}	Inadequate evidence	\N	CYP2C9*64 is assigned uncertain funciton due to inadequate evidence. The nonsynonymous variants present in CYP2C9*64 is predicted to be deleterious in both SIFT and Polyphen predictions. There are no in vitro or clinical studies reported. Consensus was not achieved among experts and therefore uncertain function was assigned.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778107	340	CYP2D6	*94	\N	Uncertain function	\N	n/a	778106	{25469868,26310775,26666748,26544071,26406933,27109434,27097346,27016952,26542054,26937172,26968424,27203132,27251229,27354764,27538917}	Inadequate	\N	CYP2D6*94 is assigned uncertain function due to inadequate evidence. In vitro studies found CYP2D6*94 demonstrated enzyme activity ranging from similar to decreased activity compared to wildtype with various substrates (25469868, 26310775, 26666748, 26544071, 26406933, 27109434, 27097346, 27016952, 26542054, 26937172, 26968424, 27203132, 27251229, 27354764, 27538917). Therefore, consensus among experts was uncertain function.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778177	340	CYP2D6	*129	\N	No function	\N	0.0	778176	{32759992}	Limited	\N	CYP2D6*129 is assigned no function based on limited evidence. CYP2D6*129 is defined by an premature stop codon predicted to yield truncated protein and thus be nonfunctional. One in vitro study demonstrated substantially decreased intrinsic clearance CLint (Vmax/Km) of 3.2% compared to *1 for tamoxifen N-desmethylation; no activity was detectable for dextromethorphan O-demethylation (32759992). Therefore, consensus among experts was no function with an activity value of 0 based on limited evidence.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
777374	210	CFTR	S1251N	\N	ivacaftor responsive	\N	\N	777373	{}	\N	\N	\N	\N	f
777705	344	CYP2C9	*19	Uncertain function	Uncertain function	\N	n/a	777704	{23752738,23844998,24118918,25142737,25476996,25144335,25951663,25614704,25832633,25884291,27163851,24077631,16099926}	Inadequate evidence	\N	CYP2C9*19 is assigned uncertain function due to inadequate evidence. One subject with CYP2C9*1/*19 genotype exhibited decreased clearance compared to wildtype subjects based on tolbutamide plasma concentrations and urine metabolite concentrations after one 500mg dose. This result correlated with the in vitro study where CYP2C9*19 demonstrated 31% enzyme activity with a tolbutamide substrate compared to wildtype (25614704). Multiple in vitro studies similarly found CYP2C9*19 demonstrated decreased clearance with various substrates compared to wildtype (23752738, 23844998, 24118918, 25142737, 25476996, 25144335, 25951663, 25832633, 25884291, 27163851, 24077631), however, one in vitro study showed CYP2C9*19 had similar activity compared to wildtype with a tolbutamide substrate (16099926). Consensus was not achieved among experts and therefore uncertain function was assigned but experts agreed additional evidence may change the assignment to decreased function.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": 0.00047686882, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
777797	326	CYP2C9	*65	Uncertain function	Uncertain function	\N	n/a	777796	{33536773}	Inadequate evidence	\N	CYP2C9*65 is assigned uncertain funciton due to inadequate evidence. The nonsynonymous variant present in CYP2C9*65 is predicted to be deleterious in both SIFT and Polyphen predictions. There are no in vitro or clinical studies reported. Consensus was not achieved among experts and therefore uncertain function was assigned.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
6235321	8	CYP2C9	*86	\N	\N	\N	\N	6235320	\N	\N	\N	\N	\N	f
778197	339	CYP2D6	*139	\N	Unknown function	\N	n/a	778196	{}	No Evidence	\N	CYP2D6*139 is assigned unknown function due to no literature describing function of this allele. Therefore, consensus among experts was unknown function due to no available evidence.	{"Latino": null, "American": 0.0, "European": 0.0, "Oceanian": null, "East Asian": 0.0, "Near Eastern": null, "Central/South Asian": 0.001, "Sub-Saharan African": 0.001, "African American/Afro-Caribbean": 0.0}	f
778201	246	CYP2D6	*141	\N	Uncertain function	\N	n/a	778200	{}	Inadequate	\N	CYP2D6*141 is assigned uncertain function due to the presence of variants found in other alleles known to cause decreased (*17) or no function (*36); there is no literature describing the combined effect of the variants found in this allele. Therefore, consensus among experts was uncertain function.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
3685519	135	RYR1	c.5360C>T	Benign	Normal function	\N	n/a	3685518	{33767344}	\N	\N	BA1	{"Latino": 0.01753, "American": 0.02632, "European": 0.02158376, "East Asian": 0.0001923, "Near Eastern": 0.029322615, "Central/South Asian": 0.04845, "Sub-Saharan African": 0.004607}	f
778452	325	DPYD	c.2195T>G	Normal function	Normal function	\N	1.0	778451	{24648345}	Limited	\N	5-fluorouracil (in vitro)	{"Latino": 0.0, "European": 0.0, "East Asian": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": 0.0019285714, "African American/Afro-Caribbean": 0.0}	f
778953	296	G6PD	Bari	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778952	{22293322,8808605,7959695}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
6235323	8	CYP2C9	*87	\N	\N	\N	\N	6235322	\N	\N	\N	\N	\N	f
6235325	8	CYP2C9	*88	\N	\N	\N	\N	6235324	\N	\N	\N	\N	\N	f
3685681	135	RYR1	c.7487C>T	Variant of uncertain significance	Uncertain function	\N	n/a	3685680	{35849058}	\N	\N	PP3_Mod	{"Latino": null, "American": null, "European": 0.0000294, "East Asian": 0.0003857, "Near Eastern": 0.001152, "Central/South Asian": 0.000207, "Sub-Saharan African": 0.00002413}	f
779425	322	TPMT	*15	\N	No function	\N	\N	779424	{15083071}	\N	\N	\N	{"Latino": 0.0, "European": 0.000045666697, "East Asian": 0.0, "Near Eastern": null, "Central/South Asian": 0.0, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778889	296	G6PD	Farroupilha	II-III/Deficient	II/Deficient	\N	\N	778888	{22293322,10627140}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
778019	340	CYP2D6	*43	\N	Uncertain function	\N	n/a	778018	{24647041,30366777}	Inadequate	\N	CYP2D6*43 is assigned uncertain function due to inadequate evidence. In vitro studies found CYP2D6*43 demonstrated enzyme activity ranging from nondetectable to similar activity compared to wildtype with various substrates (24647041, 30366777). Therefore, consensus among experts was uncertain function.	{"Latino": null, "American": 0.0, "European": 0.00058934913, "Oceanian": 0.002, "East Asian": 0.00038300423, "Near Eastern": 0.003, "Central/South Asian": 0.01, "Sub-Saharan African": 0.0100665875, "African American/Afro-Caribbean": 0.006397251}	f
778677	296	G6PD	Honiara	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778676	{22293322,7726184}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
777364	210	CFTR	R117C	\N	ivacaftor responsive	\N	\N	777363	{}	\N	\N	\N	\N	f
777366	210	CFTR	R117H	\N	ivacaftor responsive	\N	\N	777365	{}	\N	ACMG screening panel	\N	\N	f
777368	210	CFTR	R347H	\N	ivacaftor responsive	\N	\N	777367	{}	\N	\N	\N	\N	f
777370	210	CFTR	R352Q	\N	ivacaftor responsive	\N	\N	777369	{}	\N	\N	\N	\N	f
3685499	135	RYR1	c.4763C>T	Variant of uncertain significance	Uncertain function	\N	n/a	3685498	{35849058}	\N	\N	None	{"Latino": null, "American": null, "European": 0.0000588, "East Asian": null, "Near Eastern": null, "Central/South Asian": 0.0002071, "Sub-Saharan African": 0.000169}	f
777671	344	CYP2C9	*2	Decreased function	Decreased function	\N	0.5	777670	{29283396,20150829,1563752,12742136,10413320,27179628,25775139,19082874,30088221,15637526}	Definitive	\N	CYP2C9*2 is assigned decreased function based on definitive evidence in homozygous and heterozygous patients and in vitro experimental data. CYP2C9*2 has been studied for more than 20 years and its association with impaired function compared to wildtype is well-established (29283396, 20150829, 15637526). The phenotype for patients homozygous for the CYP2C9*2 variant was updated from poor metabolizer to intermediate metabolizer after reevaluation of prior and new evidence demonstrating CYP2C9*2 has more enzyme activity than CYP2C9*3, which results in in a similar phenotype for CYP2C9*1/*3 and CYP2C9 *2/*2 patients (12742136, 10413320, 27179628, 25775139, 19082874, 30088221), both of which can be distinguished from those homozygous for CYP2C9*3/*3. Therefore, consensus among experts was decreased function with an activity value of 0.5 based on definitive evidence.	{"Latino": 0.07625658, "American": 0.033402413, "European": 0.1273007, "Oceanian": 0.029310955, "East Asian": 0.0021256818, "Near Eastern": 0.12977302, "Central/South Asian": 0.11379695, "Sub-Saharan African": 0.013114594, "African American/Afro-Caribbean": 0.02243724}	f
777759	344	CYP2C9	*46	Decreased function	Decreased function	\N	0.5	777758	{24077631,24118918,25142737,25144335,25476996,25614704,25832633,25884291,25951663,25924705,27163851,23844998}	Limited	\N	CYP2C9*46 is assigned decreased function based on limited evidence in one heterozygous patient and in vitro studies. One subject with CYP2C9*1/*46 genotype exhibited increased AUC and decreased oral clearance compared to wildtype subjects based on tolbutamide plasma concentrations after one 500mg dose (25614704). Multiple in vitro studies found CYP2C9*46 demonstrated decreased clearance compared to wildtype with various substrates (24077631, 24118918, 25476996, 25832633, 25884291, 25951663, 25924705, 23844998, 25614704). Although two in vitro studies showed CYP2C9*46 had similar activity compared to wildtype, the experts did not find these results convincing as in these studies CYP2C9*2 which definitively has decreased function, demonstrated increased or similar activity compared to wildtype in these studies (25142737, 27163851). An additional in vitro study showed CYP2C9*46 had similar activity compared to wildtype (25144335), however, the experts did not find this result convincing as the function of CYP2C9*46 in vivo and in vitro demonstrated decreased function toward the majority of substrates. Therefore, consensus among experts was decreased function with an activity value of 0.5 based on limited evidence as it was determined the phenotypes containing this allele would be clinically distinct from phenotypes comprising normal function alleles.	{"Latino": 0.0, "American": null, "European": 0.0, "Oceanian": null, "East Asian": null, "Near Eastern": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
777773	344	CYP2C9	*53	Uncertain function	Uncertain function	\N	n/a	777772	{24077631,24118918,25142737,25144335,25476996,25832633,25884291,25951663,25924705,27163851,23844998}	Inadequate evidence	\N	CYP2C9*53 is assigned uncertain function due to inadequate evidence. In vitro studies found CYP2C9*53 demonstrated enzyme activity ranging from decreased to increased compared to wildtype with various substrates (24077631, 24118918, 25142737, 25144335, 25476996, 25832633, 25951663, 25884291, 25924705, 27163851, 23844998). Therefore, consensus among experts was uncertain function due to inadequate evidence.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778721	296	G6PD	Swansea	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778720	{22293322,7858267}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
777677	344	CYP2C9	*5	Decreased function	Decreased function	\N	0.5	777676	{23752738,15289788,11455026,16220110,17504998,21811894,11901091}	Strong	\N	CYP2C9*5 is assigned decreased function based on strong evidence in heterozygous patients and in vitro studies. Three subjects carrying the CYP2C9*5 allele (CYP2C9*1/*5, CYP2C9*5/*6, CYP2C9*5/*8 genotype) had decreased losartan metabolism compared to wildtype based on urinary metabolites after a single 25mg dose (15289788). Two CYP2C9 *1/*5 subjects, one CYP2C9 *5/*6 subject, and one CYP2C9*5/*8 subject had lower phenytoin metabolism compared to wildtype based on urinary excretion of a phenytoin metabolite after a single 300mg dose. Additionally, the CYP2C9 *5/*6 subject demonstrated the lowest phenytoin metabolism as the only subject of the 109 subject cohort to have a urinary metabolite concentration below the limit of quantification (16220110). One CYP2C9 *5/*8 demonstrated the lowest acenocoumarol metabolism based on plasma concentrations in a 36 subject cohort (21811894). One CYP2C9*1/*5 subject demonstrated decreased indisulam metabolism with an AUC nearly two times greater than wildtype subjects (17504998). These results correlated with in vitro pharmacokinetic studies which demonstrated decreased clearance of warfarin, diclofenac, flurbiprofen, naproxen, and piroxicam compared to wildtype (11455026, 11901091). A separate in vitro study found CYP2C9*5 has decreased enzyme activity compared to wildtype with warfarin and tolbutamide substrates that (23752738). Therefore, consensus among experts was decreased function with an activity value of 0.5 based on strong evidence.	{"Latino": 0.00871987, "American": 0.0014913112, "European": 0.00017448276, "Oceanian": null, "East Asian": 0.0, "Near Eastern": 0.00052266667, "Central/South Asian": 0.0, "Sub-Saharan African": 0.010325842, "African American/Afro-Caribbean": 0.011626912}	f
779433	322	TPMT	*19	\N	Uncertain function	\N	\N	779432	{18708949,15652243}	\N	\N	\N	{"Latino": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
777695	344	CYP2C9	*14	Decreased function	Decreased function	\N	0.5	777694	{16099926,23844998,24118918,25142737,25144335,25476996,25951663,25832633,25884291,25924705,27163851,24077631,24956244,19077919,15371982,23752738}	Moderate	\N	CYP2C9*14 is assigned decreased function based on moderate evidence in heterozygous patients and in vitro studies. Separate studies of patients on a stable dose of warfarin with CYP2C9 *1/*14 genotype required a lower warfarin dose compared to CYP2C9*1/*1 patients (24956244, 19077919, 15371982). The VKORC1 and CYP4F2 variants associated with increased warfarin dose requirements were also observed in one of these patients which further suggested decreased warfarin metabolism and warfarin dose was due to the CYP2C9 *1/*14 genotype (24956244). In vitro studies similarly found CYP2C9*14 demonstrated decreased clearance of warfarin, phenytoin, tolbutamide, glimepiride, carvedilol, propofol, flurbiprofen, mestranol, diclofenac, and losartan (23752738, 27163851, 16099926, 24077631, 24118918, 25476996, 25832633, 25144335, 25924705, 25951663, 23844998). Although two in vitro studies showed CYP2C9*14 had similar activity compared to wildtype, the experts did not find these results convincing as in these studies CYP2C9*2 and/or CYP2C9*3 which definitively have decreased function and no function, respectively, demonstrated increased activity compared to wildtype in these studies (25142737, 25884291). Therefore, consensus among experts was decreased function with an activity value of 0.5 based on moderate evidence.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": 0.00033588216, "Near Eastern": 0.001, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778189	339	CYP2D6	*135	\N	Uncertain function	\N	n/a	778188	{32759992}	Inadequate	\N	CYP2D6*135 is assigned uncertain function due to inadequate literature describing function of this allele. One in vitro study demonstrated decreased intrinsic clearance CLint (Vmax/Km) of 32.3% and 45.8% compared to *1 for tamoxifen N-desmethylation and dextromethorphan O-demethylation, respectively (32759992). Therefore, consensus among experts was uncertain function due to inadequate evidence.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
3685689	135	RYR1	c.7528T>C	Variant of uncertain significance	Uncertain function	\N	n/a	3685688	{35849058}	\N	\N	PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
777947	340	CYP2D6	*6	\N	No function	\N	0.0	777946	{10022755,7894499,7951238,7868129}	Strong	\N	CYP2D6*6 is assigned no function based on strong evidence. CYP2D6*6 has been described in subjects demonstrating decreased metabolism of various CYP2D6 substrates (10022755, 7894499, 7951238, 7868129). CYP2D6*6 is defined by a single nucleotide deletion resulting in a frameshift and premature stop codon yielding a truncated and nonfunctional protein (7894499). Therefore, consensus among experts was no function with an activity value of 0 based on strong evidence.	{"Latino": 0.0051102643, "American": 0.0025018877, "European": 0.011197059, "Oceanian": 0.0, "East Asian": 0.00015815398, "Near Eastern": 0.00543274, "Central/South Asian": 0.00040183793, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.0028887512}	f
777979	340	CYP2D6	*23	\N	Uncertain function	\N	n/a	777978	{24647041,30366777}	Inadequate	\N	CYP2D6*23 is assigned uncertain function due to inadequate evidence. In vitro studies found CYP2D6*23 demonstrated modest decreased enzyme activity compared to wildtype with tamoxifen, bufuralol, dextromethorphan, and primaquine substrates (24647041, 30366777). Consensus was not achieved among experts as data were sparse and it was not convincing the magnitude of decreased activity was clinically significant. Therefore, uncertain function was assigned.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": 0.0, "Near Eastern": 0.0, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778027	340	CYP2D6	*47	\N	No function	\N	0.0	778026	{18784265,24647041,30366777}	Limited	\N	CYP2D6*47 is assigned no function based on limited evidence. Multiple in vitro studies found CYP2D6*47 had nondetectable enzyme activity with multiple substrates (18784265, 24647041, 30366777). Therefore, consensus among experts was no function with an activity value of 0 based on limited evidence.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": 0.0003937946, "Near Eastern": 0.0, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778059	340	CYP2D6	*63	\N	Uncertain function	\N	n/a	778058	{24647041,30366777}	Inadequate	\N	CYP2D6*63 is assigned uncertain function due to inadequate evidence. In vitro studies found CYP2D6*63 demonstrated decreased enzyme activity compared to wildtype with various substrates (24647041, 30366777). Consensus was not achieved among experts as data were sparse. Therefore, uncertain function was assigned.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": 0.00028595122, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778099	340	CYP2D6	*90	\N	Uncertain function	\N	n/a	778098	{25469868,26310775,26666748,26544071,26406933,27109434,27097346,27016952,26542054,26937172,26968424,27203132,27251229,27354764,27538917}	Inadequate	\N	CYP2D6*90 is assigned uncertain function due to inadequate evidence. In vitro studies found CYP2D6*90 demonstrated enzyme activity ranging from increased to decreased activity compared to wildtype with various substrates (25469868, 26310775, 26666748, 26544071, 26406933, 27109434, 27097346, 27016952, 26542054, 26937172, 26968424, 27203132, 27251229, 27354764, 27538917). Therefore, consensus among experts was uncertain function.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778005	340	CYP2D6	*36	\N	No function	\N	0.0	778004	{7935325,18784265,9918137,16425111,24647041,30366777,16415111}	Moderate	\N	CYP2D6*36 is assigned no function based on moderate evidence in heterozygous subjects and in vitro studies. CYP2D6*36 has been described in subjects with CYP2D6 *1/*36 and CYP2D6 *2/*36 genotype demonstrating decreased metabolism and subjects with CYP2D6 *4/*36 demonstrating poor metabolism with debrisoquine and dextromethorphan substrates (9918137, 16415111). Multiple in vitro studies found CYP2D6*36 had nondetectable or markedly decreased enzyme activity compared to wildtype with various substrates (7935325, 18784265, 24647041, 30366777). Therefore, consensus among experts was no function with an activity value of 0 based on moderate evidence.	{"Latino": 0.002, "American": 0.0, "European": 0.00017518068, "Oceanian": 0.0, "East Asian": 0.011395853, "Near Eastern": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": 0.004, "African American/Afro-Caribbean": 0.005231697}	f
779747	282	CYP2D6	*45x2	\N	Increased function	\N	2.0	778022	{15768052,24647041}	Limited	\N	CYP2D6*45x2 is assigned increased function based on limited evidence. CYP2D6*45 is assigned normal function (15768052; 24647041). Therefore, consensus among experts was increased function with an activity value of 2 based on limited evidence as it was determined the phenotypes containing a duplication of this allele would demonstrate greater protein expression and enzyme activity than that of the nonduplicated allele and be clinically distinct from phenotypes comprising normal function alleles.	{"Latino": 0.0, "American": 0.0, "European": 0.0, "Oceanian": null, "East Asian": 0.0, "Near Eastern": null, "Central/South Asian": 0.0, "Sub-Saharan African": 0.001, "African American/Afro-Caribbean": 0.0010954796}	f
778101	340	CYP2D6	*91	\N	Decreased function	\N	0.25	778100	{25469868,26310775,26666748,26544071,26406933,27109434,27097346,27016952,26542054,26937172,26968424,27203132,27251229,27354764,27538917}	Limited	\N	CYP2D6*91 is assigned decreased function with an activity value of 0.25 due to limited evidence. *91 contains 2989G>A splicing SNP found in *41 (decreased function). In vitro studies found CYP2D6*91 demonstrated enzyme activity ranging from similar to decreased activity compared to wildtype with various substrates (25469868, 26310775, 26666748, 26544071, 26406933, 27109434, 27097346, 27016952, 26542054, 26937172, 26968424, 27203132, 27251229, 27354764, 27538917): however, in the cases of normal activity, the effect of the 2989G>A splice SNP found in *41 was not captured in the in vitro system utilized which may explain activity comparable to *1 or *2. Therefore, consensus among experts was decreased function based on limited evidence.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778105	340	CYP2D6	*93	\N	Uncertain function	\N	n/a	778104	{25469868,26310775,26666748,26544071,26406933,27109434,27097346,27016952,26542054,26937172,26968424,27203132,27251229,27354764,27538917}	Inadequate	\N	CYP2D6*93 is assigned uncertain function due to inadequate evidence. In vitro studies found CYP2D6*93 demonstrated decreased enzyme activity compared to wildtype with various substrates (25469868, 26310775, 26666748, 26544071, 26406933, 27109434, 27097346, 27016952, 26542054, 26937172, 26968424, 27203132, 27251229, 27354764, 27538917). Consensus was not achieved among experts as data were sparse. Therefore, uncertain function was assigned.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
3685529	135	RYR1	c.6178G>T	Benign	Normal function	\N	n/a	3685528	{33767344}	\N	\N	BA1	{"Latino": 0.05649, "American": 0.0307, "European": 0.06447168, "East Asian": 0.00443, "Near Eastern": 0.09540812, "Central/South Asian": 0.1603, "Sub-Saharan African": 0.01248}	f
3685609	135	RYR1	c.7060G>A	Likely Pathogenic	Malignant Hyperthermia associated	\N	n/a	3685608	{35849058}	\N	\N	PS4_Mod, PM1, PP1_Mod, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685851	135	RYR1	c.12413T>C	Variant of uncertain significance	Uncertain function	\N	n/a	3685850	{35849058}	\N	\N	PS4_Sup, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
5294111	48	CYP2D6	*28x2	\N	Uncertain function	\N	n/a	777988	{24647041,30366777}	Inadequate	\N	CYP2D6*28x2 was deposit into PharmVar. CYP2D6*28 is assigned uncertain function due to inadequate evidence. In vitro studies found CYP2D6*28 demonstrated enzyme activity ranging from nondetectable to similar activity compared to wildtype with various substrates (24647041, 30366777). Therefore, consensus among experts was uncertain function for CYP2D6*28. CYP2D6*28x2 is also assigned uncertain function as it cannot yet be determined what the phenotype of a duplicated allele with uncertain function would be clinically similar to.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778133	339	CYP2D6	*107	\N	Unknown function	\N	n/a	778132	{}	No Evidence	\N	CYP2D6*107 is assigned unknown function due to no literature describing function of this allele. Therefore, consensus among experts was unknown function due to no available evidence.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778135	339	CYP2D6	*108	\N	Unknown function	\N	n/a	778134	{}	No Evidence	\N	CYP2D6*108 is assigned unknown function due to no literature describing function of this allele. Therefore, consensus among experts was unknown function due to no available evidence.	{"Latino": null, "American": 0.0, "European": 0.003, "Oceanian": null, "East Asian": 0.0, "Near Eastern": null, "Central/South Asian": 0.0, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.0}	f
778137	339	CYP2D6	*109	\N	Decreased function	\N	0.25	778136	{11470994,1844820,8101460,11266079,24647041,30366777}	Limited	\N	CYP2D6*109 is assigned decreased function based on limited evidence. *109 has the 2616delAAG (also present in *9 with decreased function-PMID 1844820; 8101460; 11266079; 24647041; 30366777) and 3184G>A (V338M) which is a core SNP of *29. One study compared activity of V338M vs that of V136I (both present in *29) and found that both decrease activity in vitro (PMID 11470994). Because both variants have been shown to have decreased function in vitro, consensus of the experts was decreased function with limited evidence.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778157	339	CYP2D6	*119	\N	Decreased function	\N	0.25	778156	{11037799,15289790,17001295,17112815,19364831}	Limited	\N	CYP2D6*119 is assigned decreased function wiht an activity value of 0.25 due to limited evidence describing function of this allele. *119 contains the splice SNP 2989G>A that is also found in *41 (decreased function; 11037799; 15289790; 17001295; 17112815; 19364831). Therefore, consensus among experts was decreased function due to limited evidence.	{"Latino": null, "American": 0.0, "European": 0.0, "Oceanian": null, "East Asian": 0.001, "Near Eastern": null, "Central/South Asian": 0.0, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.0}	f
6235906	11	CYP4F2	*18	\N	\N	\N	\N	6235905	\N	\N	\N	\N	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
6235908	11	CYP4F2	*19	\N	\N	\N	\N	6235907	\N	\N	\N	\N	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
6235910	11	CYP4F2	*20	\N	\N	\N	\N	6235909	\N	\N	\N	\N	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
6235912	11	CYP4F2	*21	\N	\N	\N	\N	6235911	\N	\N	\N	\N	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778041	340	CYP2D6	*54	\N	Decreased function	\N	0.5	778040	{18784265,24647041,30366777}	Limited	\N	CYP2D6*54 is assigned decreased function based on limited evidence. Multiple in vitro studies found CYP2D6*54 had decreased enzyme activity compared to wildtype with multiple substrates (18784265, 24647041, 30366777). Therefore, consensus among experts was decreased function with an activity value of 0.5 based on limited evidence.	{"Latino": null, "American": null, "European": 0.0, "Oceanian": null, "East Asian": 0.0004402299, "Near Eastern": 0.0, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778081	340	CYP2D6	*81	\N	No function	\N	0.0	778080	{23799451}	Limited	\N	CYP2D6*81 is assigned no function based on limited evidence. CYP2D6*81 was identified in a subject demonstrating impaired enzyme activity based on experiencing adverse effects with venlafaxine and subsequently elevated nortriptyline levels (23799451). CYP2D6*81 is defined by an early stop codon yielding a truncated and nonfunctional protein. Therefore, consensus among experts was no function with an activity value of 0 based on limited evidence.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778131	340	CYP2D6	*106	\N	Uncertain function	\N	n/a	778130	{26937359,23897164}	Inadequate	\N	CYP2D6*106 is assigned uncertain function due to inadequate evidence. CYP2D6*106 is defined by a single SNP which in silico studies predict to be a benign amino acid change (26937359). An in vitro study found CYP2D6*106 demonstrated decreased enzyme activity compared to wildtype with bufuralol and dextromethorphan substrates (23897164). Consensus was not achieved among experts as data were sparse. Therefore, uncertain function was assigned.	{"Latino": null, "American": 0.001, "European": 0.0, "Oceanian": null, "East Asian": 0.0, "Near Eastern": null, "Central/South Asian": 0.0, "Sub-Saharan African": 0.015, "African American/Afro-Caribbean": 0.0}	f
3685943	135	RYR1	c.14558C>T	Variant of uncertain significance	Uncertain function	\N	n/a	3685942	{35849058}	\N	\N	PM1_Sup, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
778065	340	CYP2D6	*68	\N	No function	\N	0.0	778064	{22111604}	Limited	\N	CYP2D6*68 is assigned no function based on limited evidence. CYP2D6*68 is a CYP2D6-CYP2D7 hybrid gene similar to CYP2D6*4 which results in a nonfunctional protein (22111604). Therefore, consensus among experts was no function with an activity value of 0 based on limited evidence.	{"Latino": null, "American": 0.001, "European": 0.0, "Oceanian": null, "East Asian": 0.0, "Near Eastern": null, "Central/South Asian": 0.001, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.0}	f
777587	344	CYP2C19	*31	\N	Uncertain function	\N	\N	777586	{26153442,30464555,29098786}	Inadequate	\N	CYP2C19*31 is assigned uncertain function due to inadequate evidence. In vitro studies found CYP2C19*31 demonstrated decreased enzyme activity compared to wildtype with mephenytoin, omeprazole, voriconazole, and nebivolol substrates (26153442, 30464555, 29098786). Consensus was not achieved among experts as data were sparse and not consistent among substrates. Therefore, uncertain function was assigned.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": 0.00019440125, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
779712	282	CYP2D6	*17x2	\N	Normal function	\N	1.0	777966	{8764380,8971426,11823760}	Limited	\N	CYP2D6*17x2 is assigned normal function based on limited evidence. CYP2D6*17 is assigned decreased function based on subjects demonstrating decreased enzyme activity with various substrates (8764380, 8971426, 11823760). Therefore, consensus among experts was normal function with an activity value of 1 based on limited evidence as it was determined the phenotypes containing a duplication of this allele would demonstrate greater enzyme activity than that of the nonduplicated allele and be clinically similar to phenotypes comprising normal function alleles.	{"Latino": 0.008826584, "American": 0.0, "European": 0.0, "Oceanian": null, "East Asian": 0.0, "Near Eastern": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": 0.002, "African American/Afro-Caribbean": 0.0019977347}	f
778055	340	CYP2D6	*61	\N	Uncertain function	\N	n/a	778054	{24647041,30366777}	Inadequate	\N	CYP2D6*61 is assigned uncertain function due to inadequate evidence. In vitro studies have found CYP2D6*61 demonstrated decreased to no detectable enzyme activity compared to wildtype with various substrates (24647041, 30366777) but consensus among experts was uncertain function.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": 0.0, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778087	340	CYP2D6	*84	\N	Uncertain function	\N	n/a	778086	{28290770}	Inadequate	\N	CYP2D6*84 is assigned uncertain function due to inadequate evidence. A subject with CYP2D6 *12/*84 demonstrated decreased dextromethorphan metabolism based on urine metabolites (28290770). Consensus was not achieved among experts as data were sparse. Therefore, uncertain function was assigned.	{"Latino": null, "American": 0.0, "European": 0.0, "Oceanian": null, "East Asian": 0.0, "Near Eastern": null, "Central/South Asian": 0.0, "Sub-Saharan African": 0.001, "African American/Afro-Caribbean": 0.003}	f
778181	339	CYP2D6	*131	\N	Uncertain function	\N	n/a	778180	{32759992}	Inadequate	\N	CYP2D6*131 is assigned uncertain function due to inadequate literature describing function of this allele. One in vitro study demonstrated substantially decreased intrinsic clearance CLint (Vmax/Km) of 3.8% and 2.3% compared to *1 for tamoxifen N-desmethylation and dextromethorphan O-demethylation, respectively. Therefore, consensus among experts was uncertain function due to inadequate evidence.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778193	339	CYP2D6	*137	\N	Uncertain function	\N	n/a	778192	{32759992}	Inadequate	\N	CYP2D6*137 is assigned uncertain function due to inadequate literature describing function of this allele. One in vitro study demonstrated decreased intrinsic clearance CLint (Vmax/Km) of 50.1% and 78.2% compared to *1 for tamoxifen N-desmethylation and dextromethorphan O-demethylation, respectively (32759992). Therefore, consensus among experts was uncertain function due to inadequate evidence.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
2091255	244	CYP2D6	*161	\N	No function	\N	0.0	2091254	{}	limited	\N	CYP2D6*161 is assigned no function based on limited evidence. CYP2D6*161 is defined by the two SNPs defining the normal function *2 allele and two SNP that are only found on this star allele of which one, 2591_2592insT causes a premature stop codon (E273X) that likely renders the allele nonfunctional.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": 0.00208, "African American/Afro-Caribbean": null}	f
778388	327	DPYD	c.1260T>A	Normal function	Normal function	\N	1.0	778387	{24648345}	Limited	\N	5-fluorouracil (in vitro)	{"Latino": 0.0, "European": 0.0005544641, "East Asian": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.0}	f
3685791	135	RYR1	c.10891G>T	Variant of uncertain significance	Uncertain function	\N	n/a	3685790	{35849058}	\N	\N	PS4_Sup, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685797	135	RYR1	c.11126C>T	Variant of uncertain significance	Uncertain function	\N	n/a	3685796	{35849058}	\N	\N	PS4_Sup	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
6237970	8	SLCO1B1	*50	\N	\N	\N	\N	6237969	\N	\N	\N	\N	\N	f
6237972	8	SLCO1B1	*51	\N	\N	\N	\N	6237971	\N	\N	\N	\N	\N	f
6237974	8	SLCO1B1	*52	\N	\N	\N	\N	6237973	\N	\N	\N	\N	\N	f
6237976	8	SLCO1B1	*53	\N	\N	\N	\N	6237975	\N	\N	\N	\N	\N	f
778139	339	CYP2D6	*110	\N	Uncertain function	\N	n/a	778138	{31368850}	Inadequate	\N	CYP2D6*110 is assigned uncertain function. CYP2D6*110 is defined by a SNP which in silico studies predict to be a deleterious amino acid change (31368850). Consensus was not achieved among experts as data were sparse. Therefore, uncertain function was assigned.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
779740	282	CYP2D6	*41x2	\N	Decreased function	\N	0.5	778014	{11037799,15289790,17001295,17112815,19364831}	Limited	\N	CYP2D6*41x2 is assigned decreased function based on limited evidence. CYP2D6*41 is assigned decreased function based on decreased protein expression and enzyme activity (11037799, 15289790, 17112815, 19364831, 17001295). Therefore, consensus among experts was decreased function with an activity value of 0.5 based on limited evidence as it was determined the phenotypes containing a duplication of this allele would demonstrate greater protein expression and enzyme activity than that of the nonduplicated allele and be clinically similar to phenotypes comprising decreased function alleles.	{"Latino": 0.00008218229, "American": 0.0, "European": 0.00033715033, "Oceanian": 0.0, "East Asian": 0.00022746579, "Near Eastern": 0.004381261, "Central/South Asian": 0.00049214147, "Sub-Saharan African": 0.00042204256, "African American/Afro-Caribbean": 0.00059508317}	f
2899153	133	CYP2B6	*44	\N	Uncertain function	\N	\N	2899152	{38596098}	Inadequate	\N	CYP2B6*44 (c.304G>A, p.A102T) – Uncertain function: CYP2B6*44 is assigned uncertain function due to inadequate evidence describing function. A single in vitro study reported decreased function for p.A102T using buproprion and efavirez as probes (38596098).	{"Latino": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778033	340	CYP2D6	*50	\N	Decreased function	\N	0.5	778032	{18784265,24647041,30366777}	Limited	\N	CYP2D6*50 is assigned decreased function based on limited evidence. Multiple in vitro studies found CYP2D6*50 had decreased enzyme activity compared to wildtype with multiple substrates (18784265, 24647041, 30366777). Therefore, consensus among experts was decreased function with an activity value of 0.5 based on limited evidence.	{"Latino": null, "American": null, "European": 0.0, "Oceanian": null, "East Asian": 0.00039791822, "Near Eastern": 0.0, "Central/South Asian": null, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": null}	f
777555	344	CYP2C19	*12	\N	Uncertain function	\N	\N	777554	{12464799}	Inadequate	\N	CYP2C19*12 is assigned uncertain function due to inadequate evidence. In one in vitro study CYP2C19*12 was poorly expressed and enzyme activity could not be assessed with a mephenytoin substrate (12464799). CYP2C19*12 is defined by the conversion of the stop codon to cysteine, and it is unclear if this protein is unstable in vivo. Therefore, consensus among experts was not achieved and uncertain function was assigned.	{"Latino": 0.0, "American": null, "European": 0.0, "Oceanian": null, "East Asian": 0.000108813925, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.0011203007}	f
778067	340	CYP2D6	*69	\N	No function	\N	0.0	778066	{18797858}	Limited	\N	CYP2D6*69 is assigned no function based on limited evidence. CYP2D6*69 was identified in a subject demonstrating poor dextromethorphan metabolism (18797858). CYP2D6*69 is a rare allele defined by several SNPs including two which are attributed to the decreased function in other CYP2D6 alleles. Therefore, consensus among experts was no function with an activity value of 0 based on limited evidence.	{"Latino": null, "American": 0.0, "European": 0.001, "Oceanian": null, "East Asian": 0.010007915, "Near Eastern": 0.0, "Central/South Asian": 0.002, "Sub-Saharan African": 0.001, "African American/Afro-Caribbean": 0.0}	f
778079	340	CYP2D6	*75	\N	Uncertain function	\N	n/a	778078	{24647041,26652007,30366777}	Inadequate	\N	CYP2D6*75 is assigned uncertain function due to inadequate evidence. In vitro studies found CYP2D6*75 demonstrated decreased enzyme activity compared to wildtype with various substrates (26652007, 24647041, 30366777). Consensus was not achieved among experts as data were sparse. Therefore, uncertain function was assigned.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": 0.00029222333, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778119	340	CYP2D6	*100	\N	No function	\N	0.0	778118	{23394389}	Limited	\N	CYP2D6*100 is assigned no function based on limited evidence. CYP2D6*100 has been described in a subject with CYP2D6*5/*100 genotype demonstrating markedly decreased dextromethorphan metabolism compared to wildtype (23394389). CYP2D6*100 is defined by the same SNPs as CYP2D6*10 in addition to a base pair deletion resulting in a frameshift yielding a nonfunctional protein. Therefore, consensus among experts was no function with an activity value of 0 based on limited evidence.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": 0.003, "Sub-Saharan African": null, "African American/Afro-Caribbean": 0.0}	f
1406322	326	CYP2C9	*75	Unknown function	Unknown function	\N	n/a	1406321	{}	No evidence	\N	CYP2C9*75 is assigned unknown function due to no literature describing function of this allele. Therefore, consensus among experts was unknown function due to no available evidence.	{"Latino": 0.0, "American": null, "European": 0.0, "Oceanian": null, "East Asian": null, "Near Eastern": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
6237978	8	SLCO1B1	*54	\N	\N	\N	\N	6237977	\N	\N	\N	\N	\N	f
778023	340	CYP2D6	*45	\N	Normal function	\N	1.0	778022	{15768052,24647041,30366777}	Limited	\N	CYP2D6*45 is assigned normal function based on limited evidence. Subjects with CYP2D6 *5/*45 genotype demonstrated similar dextromethorphan metabolism compared to wildtype subjects (15768052). In vitro studies found CYP2D6*45 demonstrated similar activity compared to wildtype with dextromethorphan and bufuralol substrates (15768052, 24647041). Although one in vitro study found CYP2D6*45 demonstrated decreased clearance compared to wildtype with a primaquine substrate (30366777) the experts did not find this result convincing as CYP2D6*45 demonstrated similar activity compared to wildtype towards a majority of substrates as well as in vivo. Therefore, consensus among experts was normal function with an activity value of 1 based on limited evidence.	{"Latino": null, "American": 0.003, "European": 0.0, "Oceanian": null, "East Asian": 0.0, "Near Eastern": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": 0.038135953, "African American/Afro-Caribbean": 0.05011446}	f
779688	286	CYP2D6	*1x2	\N	Increased function	\N	2.0	777936	{7616439,9012401}	Limited	\N	CYP2D6*1x2 is assigned increased function based on limited evidence. Subjects with CYP2D6 gene duplications demonstrated increased enzyme activity with the greatest debrisoquine metabolism among 270 subjects based on urine metabolites (7616439). Additionally, debrisoquine metabolism correlated with the number of functional CYP2D6 genes (7616439, 9012401). Therefore, consensus among experts was increased function with an activity value of 2 based on limited evidence as it was determined the phenotypes containing this allele would be clinically distinct from phenotypes comprising normal function alleles.	{"Latino": 0.015091962, "American": 0.025994705, "European": 0.008242789, "Oceanian": 0.118886255, "East Asian": 0.0033543645, "Near Eastern": 0.031482305, "Central/South Asian": 0.005793713, "Sub-Saharan African": 0.0057788896, "African American/Afro-Caribbean": 0.007974796}	f
779699	282	CYP2D6	*6x2	\N	No function	\N	0.0	777946	{7894499,7951238}	Limited	\N	CYP2D6*6x2 is assigned no function based on limited evidence. CYP2D6*6 is defined by a single nucleotide deletion resulting in a frameshift and premature stop codon yielding a truncated and nonfunctional protein (7894499). Therefore, consensus among experts was no function with an activity value of 0 based on limited evidence as it was determined the phenotypes containing a duplication of this allele would be clinically similar to phenotypes comprising the nonduplicated allele.	{"Latino": 0.00011035591, "American": 0.0, "European": 0.0, "Oceanian": null, "East Asian": 0.0, "Near Eastern": 0.0, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": 0.000067795685}	f
777997	340	CYP2D6	*32	\N	Decreased function	\N	0.25	777996	{24647041,30366777}	Limited	\N	CYP2D6*32 is assigned decreased function with an activity value of 0.25 due to limited evidence. In vitro studies found CYP2D6*32 demonstrated enzyme activity ranging from nondetectable to decreased activity compared to wildtype with various substrates (24647041, 30366777). *32 also contains 2989G>A which is the core SNP of *41 with decreased function and the only other SNP of concern, 3854G>A (E410K) would not be expected to change function as the *27 allele (defined by 3854G>A (E410K)) is normal function. Therefore, consensus among experts was decreased function with limited evidence.	{"Latino": null, "American": 0.0, "European": 0.003, "Oceanian": null, "East Asian": 0.0, "Near Eastern": 0.0, "Central/South Asian": 0.002, "Sub-Saharan African": 0.0004385813, "African American/Afro-Caribbean": 0.0}	f
778053	339	CYP2D6	*60	\N	No function	\N	0.0	778052	{19364831}	Limited	\N	CYP2D6*60 is assigned no function based on limited evidence. CYP2D6*60 is defined by an early stop codon suggesting a complete functional protein is not formed (19364831). Therefore, consensus among experts was no function with an activity value of 0 based on limited evidence.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": 0.0014483429, "Near Eastern": 0.0, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778071	340	CYP2D6	*71	\N	Uncertain function	\N	n/a	778070	{24647041,30366777}	Inadequate	\N	CYP2D6*71 is assigned uncertain function due to inadequate evidence. In vitro studies found CYP2D6*71 demonstrated decreased enzyme activity compared to wildtype with various substrates (24647041, 30366777). Consensus was not achieved among experts as data were sparse. Therefore, uncertain function was assigned.	{"Latino": null, "American": 0.0, "European": 0.0, "Oceanian": 0.042666666, "East Asian": 0.0020697587, "Near Eastern": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.0}	f
2091241	244	CYP2D6	*154	\N	Uncertain function	\N	n/a	2091240	{}	Inadequate	\N	CYP2D6*154 is assigned uncertain function due to inadequate evidence. CYP2D6*154 is defined by the three SNPs defining the decreased function *17 allele and one additional SNP that defines *75 which is classified as uncertain function.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": 0.00052, "African American/Afro-Caribbean": null}	f
778141	339	CYP2D6	*111	\N	Uncertain function	\N	n/a	778140	{31368850}	Inadequate	\N	CYP2D6*111 is assigned uncertain function. CYP2D6*111 is defined by a SNP which in silico studies predict to be a deleterious amino acid change (31368850). Consensus was not achieved among experts as data were sparse. Therefore, uncertain function was assigned.	{"Latino": null, "American": 0.0, "European": 0.004, "Oceanian": null, "East Asian": 0.0, "Near Eastern": null, "Central/South Asian": 0.008, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.0}	f
778195	340	CYP2D6	*138	\N	Uncertain function	\N	n/a	778194	{31536170}	Inadequate	\N	CYP2D6*138 is assigned uncertain function due to inadequate evidence. CYP2D6*138 is defined by a splice defect known to decrease activity and an amino acid substitution which an in vitro study found to increase activity compared to *1 when expressed on its own (31536170). Therefore, consensus among experts was uncertain function.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
6610099	2	CYP2D6	*13+*1	\N	Normal function	\N	1.0	6610098	{}	\N	\N	\N	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778831	296	G6PD	Durham	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778830	{22293322,9290617}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
779417	322	TPMT	*11	\N	No function	\N	\N	779416	{18708949,12835738,16220112}	\N	\N	\N	{"Latino": null, "European": 0.00024325753, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
2899161	133	CYP2B6	*48	\N	Uncertain function	\N	\N	2899160	{38596098}	Inadequate	\N	CYP2B6*48 (c.1145T>A, p.I382N) – Uncertain function: CYP2B6*48 is assigned uncertain function due to inadequate evidence describing function. A single in vitro study reported decreased function for p.I382N using buproprion and efavirez as probes (38596098).	{"Latino": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
779423	322	TPMT	*14	\N	No function	\N	\N	779422	{18708949,15083071}	\N	\N	\N	{"Latino": null, "European": 0.0, "East Asian": 0.0, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": null}	f
777987	340	CYP2D6	*27	\N	Normal function	\N	1.0	777986	{18784265,18838503,24647041,30366777}	Limited	\N	CYP2D6*27 is assigned normal function based on limited evidence. Multiple in vitro studies found CYP2D6*27 demonstrated similar activity compared to wildtype with various substrates (18784265, 18838503). Although some in vitro studies found CYP2D6*27 demonstrated modestly decreased activity it was not convincing the magnitude of decreased activity was clinically significant (24647041, 30366777). Therefore, consensus among experts was normal function with an activity value of 1 based on limited evidence as it was determined the phenotypes containing this allele would be clinically similar to phenotypes comprising normal function alleles.	{"Latino": null, "American": 0.003, "European": 0.0, "Oceanian": null, "East Asian": 0.00056961953, "Near Eastern": 0.007, "Central/South Asian": 0.0, "Sub-Saharan African": 0.0033542388, "African American/Afro-Caribbean": 0.003}	f
6610100	2	CYP2D6	*13+*1x2	\N	Increased function	\N	2.0	6610098	{}	\N	\N	\N	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
6610102	2	CYP2D6	*13+*2	\N	Normal function	\N	1.0	6610101	{}	\N	\N	\N	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
6610104	2	CYP2D6	*13+*68x2+*4	\N	No function	\N	0.0	6610103	{}	\N	\N	\N	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
779744	282	CYP2D6	*43x2	\N	Uncertain function	\N	n/a	778018	{24647041,30366777}	Inadequate	\N	CYP2D6*43x2 is assigned uncertain function due to inadequate evidence. CYP2D6*43 is assigned uncertain function due to inconsistent findings regarding enzyme activity compared to wildtype (24647041, 30366777). Therefore, consensus among experts was uncertain function as it cannot yet be determined what the phenotype of a duplicated allele with uncertain function would be clinically similar to.	{"Latino": null, "American": 0.001, "European": 0.0, "Oceanian": null, "East Asian": 0.0, "Near Eastern": null, "Central/South Asian": 0.0, "Sub-Saharan African": 0.001, "African American/Afro-Caribbean": 0.0}	f
778089	339	CYP2D6	*85	\N	Unknown function	\N	n/a	778088	{}	No Evidence	\N	CYP2D6*85 is assigned unknown function due to no literature describing function of this allele. Therefore, consensus among experts was unknown function due to no available evidence.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": 0.0, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778091	339	CYP2D6	*86	\N	Unknown function	\N	n/a	778090	{}	No Evidence	\N	CYP2D6*86 is assigned unknown function due to no literature describing function of this allele. Therefore, consensus among experts was unknown function due to no available evidence.	{"Latino": null, "American": 0.0, "European": 0.0, "Oceanian": null, "East Asian": 0.0001941358, "Near Eastern": null, "Central/South Asian": 0.021387372, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.0}	f
778121	340	CYP2D6	*101	\N	No function	\N	0.0	778120	{23394389}	Limited	\N	CYP2D6*101 is assigned no function based on limited evidence. CYP2D6*101 has been described in a subject with CYP2D6*2/*101 genotype demonstrating markedly decreased dextromethorphan metabolism compared to wildtype (23394389). CYP2D6*101 is defined by the same SNPs as CYP2D6*10 in addition to a 19 base pair deletion resulting in a frameshift yielding a nonfunctional protein. Therefore, consensus among experts was no function with an activity value of 0 based on limited evidence.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": 0.003, "Sub-Saharan African": null, "African American/Afro-Caribbean": 0.0}	f
6610097	2	CYP2D6	*36+*10	\N	Decreased function	\N	0.25	6610096	{}	\N	\N	\N	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
6610106	2	CYP2D6	*36x2+*10	\N	Decreased function	\N	0.25	6610105	{}	\N	\N	\N	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
6610095	2	CYP2D6	*68+*4	\N	No function	\N	0.0	6610094	{}	\N	\N	\N	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778354	331	DPYD	c.601A>C	No function	No function	\N	0.0	778353	{24648345}	Limited	\N	5-fluorouracil (in vitro)	{"Latino": 0.0, "European": 0.00004094045, "East Asian": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778691	296	G6PD	Kozukata	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778690	{22293322,9410474}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
778673	296	G6PD	Lages	III/Deficient	III/Deficient	\N	\N	778672	{22293322,9526168}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
777599	344	CYP2C19	*37	\N	No function	\N	\N	777598	{31260137}	Limited	\N	CYP2C19*37 is assigned no function based on limited evidence. CYP2C19*37 is a partial deletion of the CYP2C19 gene and was identified by interrogation of multiple databases of clinical chromosomal microarray data (31260137). Therefore, because a partial gene deletion is not expected to result in a functional protein, consensus among experts was no function based on limited evidence as it was determined the phenotypes containing this allele would be clinically distinct from phenotypes comprising normal function and decreased function alleles.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
777791	326	CYP2C9	*62	No function	Uncertain function	\N	n/a	777790	{32531309}	Inadequate evidence	\N	CYP2C9*62 is assigned uncertain funciton due to inadequate evidence. One in vitro study found the protein expression of CYP2C9*62 was significantly lower than that of the wild-type, and its metabolic activity was also significantly decreased after the addition of three typical CYP2C9 probe drugs (tolbutaminde, losartan, and diclofenac), suggesting that the new mutant can dramatically affect the metabolism of CYP2C9 drugs in vitro (32531309). Consensus was not achieved among experts and therefore uncertain function was assigned.	{"Latino": 0.00010, "American": null, "European": 0.00010, "Oceanian": null, "East Asian": null, "Near Eastern": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778093	340	CYP2D6	*87	\N	Uncertain function	\N	n/a	778092	{25469868,26310775,26666748,26544071,26406933,27109434,27097346,27016952,26542054,26937172,26968424,27203132,27251229,27354764,27538917}	Inadequate	\N	CYP2D6*87 is assigned uncertain function due to inadequate evidence. In vitro studies found CYP2D6*87 demonstrated enzyme activity ranging from increased to decreased activity compared to wildtype with various substrates (25469868, 26310775, 26666748, 26544071, 26406933, 27109434, 27097346, 27016952, 26542054, 26937172, 26968424, 27203132, 27251229, 27354764, 27538917). Therefore, consensus among experts was uncertain function.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
6610107	2	CYP2D6	*36+*10x2	\N	Decreased function	\N	0.5	6610096	{}	\N	\N	\N	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778789	296	G6PD	Nankang	II/Deficient	II/Deficient	\N	\N	778788	{22293322,8807322,16329560}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": 0.0, "European": 0.0, "East Asian": 0.00014430014, "Central/South Asian": 0.0, "African American/Afro-Caribbean": 0.0}	f
6610110	2	CYP2D6	*36x2+*10x2	\N	Decreased function	\N	0.5	6610105	{}	\N	\N	\N	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
6610109	2	CYP2D6	*68+*2	\N	Normal function	\N	1.0	6610108	{}	\N	\N	\N	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778973	296	G6PD	Kawasaki	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778972	{22293322,1945893}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
3685735	135	RYR1	c.8654C>G	Variant of uncertain significance	Uncertain function	\N	n/a	3685734	{35849058}	\N	\N	None	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
778394	327	DPYD	c.1314T>G	Decreased function	Decreased function	\N	0.5	778393	{24648345}	Limited	\N	5-fluorouracil (in vitro)	{"Latino": 0.0, "European": 0.0, "East Asian": 0.00068351155, "Central/South Asian": 0.0, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.0}	f
778939	296	G6PD	Beverly Hills, Genova, Iwate, Niigata, Yamaguchi	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778938	{22293322,7440223,2307454,9192788}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
778671	296	G6PD	Sinnai	III/Deficient	III/Deficient	\N	\N	778670	{22293322,10627140}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
778817	296	G6PD	Cincinnati	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778816	{22293322,20949590}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
778805	296	G6PD	Coimbra Shunde	II/Deficient	II/Deficient	\N	\N	778804	{22293322,1551674,8471773}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": 0.0, "European": 0.000010230493, "East Asian": 0.00007214487, "Central/South Asian": 0.00020966558, "African American/Afro-Caribbean": 0.0}	f
778903	296	G6PD	Mira d'Aire	IV/Normal	IV/Normal	\N	\N	778902	{22293322,1945893}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": 0.00060634164, "European": 0.000009038323, "East Asian": 0.0, "Central/South Asian": 0.0, "African American/Afro-Caribbean": 0.00037544584}	f
778863	296	G6PD	Papua	Uncertain	Uncertain function	\N	\N	778862	{22293322,9410474}	Inadequate	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
778803	296	G6PD	Pedoplis-Ckaro	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778802	{22293322,18066402}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
778761	296	G6PD	Quing Yan	III/Deficient	III/Deficient	\N	\N	778760	{22293322,8471773}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
778821	296	G6PD	Radlowo	II/Deficient	II/Deficient	\N	\N	778820	{22293322,10571945}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
778683	296	G6PD	Rignano	III/Deficient	III/Deficient	\N	\N	778682	{22293322,17524386}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
778731	296	G6PD	Sierra Leone	III/Deficient	III/Deficient	\N	\N	778730	{22293322,32387609,18452027}	Inadequate	\N	Function assigned based on evidence supporting decreased enzyme activity resulting in a WHO class III assignment (32387609).	{"Latino": 0.000035720663, "European": 0.0025682764, "East Asian": 0.0, "Central/South Asian": 0.00031527507, "African American/Afro-Caribbean": 0.00015804447}	f
778707	296	G6PD	Songklanagarind	II/Deficient	II/Deficient	\N	\N	778706	{22293322,15727905}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
778967	296	G6PD	Suwalki	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778966	{22293322,14757424}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
777799	326	CYP2C9	*66	Uncertain function	Uncertain function	\N	n/a	777798	{33536773}	Inadequate evidence	\N	CYP2C9*66 is assigned uncertain funciton due to inadequate evidence. The nonsynonymous variant present in CYP2C9*66 is predicted to be tolerated in SIFT and benign in Polyphen predictions. There are no in vitro or clinical studies reported. Consensus was not achieved among experts and therefore uncertain function was assigned.	{"Latino": 0.0, "American": null, "European": 0.0, "Oceanian": null, "East Asian": null, "Near Eastern": 0.0, "Central/South Asian": 0.00080, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778420	327	DPYD	c.1679T>G (*13)	No function	No function	\N	0.0	778419	{23328581}	Moderate	\N	5-fluorouracil (in vitro)	{"Latino": 0.0, "European": 0.00055783015, "East Asian": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.0}	f
3827885	117	MT-RNR1	m.827A>G	\N	normal risk of aminoglycoside-induced hearing loss	\N	\N	3827884	{16782057,18261986,18830133,20353758}	Limited	\N	MT-RNR1 827A>G is assigned a normal risk of aminoglycoside-induced hearing loss based on limited evidence. There are weak evidence proposing an association with aminoglycoside-induced hearing loss (16782057, 18261986, 20353758). However, there is one study showing patients with 827A>G mutation with a history of exposure to aminoglycosides with normal hearing (18830133) and this variant has too high a population frequency in certain haplogroups to be classified as associated with aminoglycoside-induced hearing loss. Therefore, consensus among experts was this variant is associated with normal risk of aminoglycoside-induced hearing loss based on limited evidence.	{"European": 0.0017502992, "East Asian": 0.035319928, "Near Eastern": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": 0.0}	f
3827919	117	MT-RNR1	m.1556C>T	\N	uncertain risk of aminoglycoside-induced hearing loss	\N	\N	3827918	{15141753}	Inadequate evidence	\N	MT-RNR1 1556C>T is assigned an uncertain risk of aminoglycoside-induced hearing loss based on inadequate evidence. Case report of of a patient with streptomycin-induced tinnitus carrying this variant (15141753) . Therefore, consensus among experts was uncertain risk of aminoglycoside-induced hearing loss due to insufficient evidence.	{"European": 0.000031612555, "East Asian": 0.0, "Near Eastern": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": null}	f
3685409	135	RYR1	c.1202G>A	Pathogenic	Malignant Hyperthermia associated	\N	n/a	3685408	{35849058}	\N	\N	PS3_Mod, PS4, PM1, PP1, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
778083	339	CYP2D6	*82	\N	Unknown function	\N	n/a	778082	{}	No Evidence	\N	CYP2D6*82 is assigned unknown function due to no literature describing function of this allele. Therefore, consensus among experts was unknown function due to no available evidence.	{"Latino": 0.021, "American": 0.009419355, "European": 0.0, "Oceanian": null, "East Asian": 0.0, "Near Eastern": 0.0, "Central/South Asian": 0.00089590444, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.0}	f
778438	325	DPYD	c.1905+1G>A (*2A)	No function	No function	\N	0.0	778437	{23328581}	Strong	This rsID, when combined with rs1801159, makes up DPYD*2B	5-fluorouracil (in vitro)	{"Latino": 0.00078298897, "European": 0.007917321, "East Asian": 0.0, "Central/South Asian": 0.005076194, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.0031082802}	f
779007	296	G6PD	Amiens	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	779006	{22293322,22139979}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
6481209	6	NAT2	*19	Slow	Decreased function	\N	\N	6481208	{18680467,12222688,9173883}	Limited	\N	NAT2*19 is assigned decreased function based on limited evidence. The NAT gene nomenclature committee has historically assigned acetylation activity to alleles as either "rapid" or "slow", classifying the NAT2*19 allele as "slow" . Under the CPIC allele function terminology, slow acetylation alleles are categorized as "Decreased Function". NAT2*19 is characterized by the core SNVs c.190C>T (p.R64W) and c.803G>A (p.R268K). c.803G>A defines NAT2*4, formerly considered the reference allele, which has repeatedly exhibited increased function in vivo and in vitro. In vitro studies of c.190C>T (p.R64W) have shown decreased protein expression, decreased thermostability, and significantly decreased N-acetyltransferase activity toward sulfamethazine (12222688). An additional in vitro study found that amino acid substitutions of arginine 64 to alanine, lysine, methionine, or glutamine (the latter of which defines NAT2*14) significantly decreased NAT2 protein stability and N-acetyltransferase activity toward p-aminosalicylic acid and all but p.R64K showed decreased N-acetyltransferase activity toward sulfamethazine (9173883). These results highlight the importance of the p.R64 residue for proper NAT2 catalytic activity. Published in silico modeling predicts that c.190C>T (p.R64W) decreases NAT2 protein stability, decreases flexibility and hydrogen bond capacity, and increases hydrophobicity and aromaticity resulting in a loss of electrostatic interactions (18680467). Similarly, six out of nine variant effect predictors tested by CPIC staff predict that c.190C>T (p.R64W) impairs NAT2 protein function.	\N	f
778127	339	CYP2D6	*104	\N	Unknown function	\N	n/a	778126	{}	No Evidence	\N	CYP2D6*104 is assigned unknown function due to no literature describing function of this allele. Therefore, consensus among experts was unknown function due to no available evidence.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": 0.0, "Near Eastern": 0.0033, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778408	327	DPYD	c.1519G>A	Normal function	Normal function	\N	1.0	778407	{24648345}	Limited	\N	5-fluorouracil (in vitro)	{"Latino": 0.0, "European": 0.000013648505, "East Asian": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778410	327	DPYD	c.1543G>A	Normal function	Normal function	\N	1.0	778409	{24648345}	Limited	\N	5-fluorouracil (in vitro)	{"Latino": 0.0, "European": 0.00009100371, "East Asian": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778412	327	DPYD	c.1577C>G	Normal function	Normal function	\N	1.0	778411	{24648345}	Limited	\N	5-fluorouracil (in vitro)	{"Latino": 0.0003390512, "European": 0.0, "East Asian": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.0}	f
778414	327	DPYD	c.1601G>A (*4)	Normal function	Normal function	\N	1.0	778413	{23588312}	Moderate	\N	5-fluorouracil (ex vivo)	{"Latino": 0.009438756, "European": 0.019760394, "East Asian": 0.0, "Central/South Asian": 0.008595228, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.009713376}	f
6355218	9	CFTR	A349V	\N	ivacaftor responsive	\N	\N	6355217	{}	\N	\N	\N	\N	f
777435	344	CYP2B6	*7	Decreased function	Decreased function	\N	\N	777434	{12642465,14551287,18171905,21659470,24260284,30201214,31324697,32238417,35538637,3553863}	Limited	\N	CYP2B6*7 (c.516G>T, p.Q172H/splice defect; c.785A>G, p.K262R and c.1459C>T, p.R487C) - Decreased function: CYB2B6*7 is assigned decreased function. CYP2B6*7 contains the variants which define CYP2B6*6 in addition to a third SNP (c.1459C>T). Since this is a rare variant, there are no data from human liver microsomes or clinical trials regarding its function. Data from several in vitro expression systems are inconclusive: some studies show decreased activity (31324697, 32238417, 3553863) while others exhibit increased activity (12642465, 21659470, 30201214). This discrepancy is probably due to differences in the in vitro expression systems and substrates used. As is the same for *6, the mechanism for decreased activity is aberrant splicing caused by c.516G>T, which leads to reduced amounts of protein and thus, activity (14551287, 18171905, 24260284). As a result, alleles having c.516G>T are considered decreased function, regardless of the functional status of additional other variants unless these cause no function (e.g., CYP2B6*13 and CYP2B6*38). Therefore, the consensus among experts was decreased function based on the presence of c.516G>T and limited evidence.	{"Latino": 0.008, "European": 0.024807692, "Oceanian": 0.01, "East Asian": 0.0, "Near Eastern": 0.024, "Central/South Asian": null, "Sub-Saharan African": 0.016, "African American/Afro-Caribbean": 0.0}	f
778069	340	CYP2D6	*70	\N	Uncertain function	\N	n/a	778068	{24647041,30366777}	Inadequate	\N	CYP2D6*70 is assigned uncertain function due to inadequate evidence. In vitro studies found CYP2D6*70 demonstrated decreased enzyme activity compared to wildtype with various substrates (24647041, 30366777) but consensus among experts was uncertain function.	{"Latino": null, "American": null, "European": 0.0, "Oceanian": null, "East Asian": 0.0, "Near Eastern": 0.0, "Central/South Asian": null, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": null}	f
777745	344	CYP2C9	*39	No function	No function	\N	0.0	777744	{24077631,24118918,25142737,25144335,25476996,25832633,25951663,25884291,27163851,23844998}	Limited	\N	CYP2C9*39 is assigned no function based on limited evidence. Multiple in vitro studies found CYP2C9*39 demonstrated decreased clearance with numerous substrates compared to wildtype (24077631, 24118918, 25142737, 25144335, 25476996, 25832633, 25951663, 25884291, 27163851, 23844998). Therefore, consensus among experts was no function with an activity value of 0 based on limited evidence as it was determined the phenotypes containing this allele would be clinically distinct from phenotypes comprising normal function or decreased function alleles.	{"Latino": 0.0, "American": null, "European": 0.0, "Oceanian": null, "East Asian": null, "Near Eastern": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778430	325	DPYD	c.1796T>C	Normal function	Normal function	\N	1.0	778429	{24648345}	Limited	\N	5-fluorouracil (in vitro)	{"Latino": 0.0, "European": 0.000090990965, "East Asian": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778432	325	DPYD	c.1896T>C	Normal function	Normal function	\N	1.0	778431	{23588312}	Moderate	\N	5-fluorouracil (ex vivo)	{"Latino": 0.08113257, "European": 0.03787994, "East Asian": 0.12373856, "Central/South Asian": 0.03587631, "Sub-Saharan African": 0.007970238, "African American/Afro-Caribbean": 0.03187898}	f
778434	325	DPYD	c.1898delC (*3)	No function	No function	\N	0.0	778433	{24648345}	Moderate	\N	5-fluorouracil (in vitro)	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
6481225	6	NAT2	*34	Slow	Decreased function	\N	\N	6481224	{28523442,9154882,15558239,17011540,28959610}	Definitive	\N	NAT2*34 is assigned decreased function based on definitive evidence. The NAT gene nomenclature committee has historically assigned acetylation activity to alleles as either "rapid" or "slow", classifying the NAT2*34 allele as "slow" . Under the CPIC allele function terminology, slow acetylation alleles are categorized as "Decreased Function". NAT2*34 is characterized by the core SNV c.590G>A (p.R197Q) which has been studied for more than 25 years and has shown decreased NAT2 N-acetylation activity in numerous in vivo and in vitro studies using various substrates. In vivo phenotyping studies have demonstrated that individuals heterozygous for NAT2*34 in combination with another decreased function allele exhibit decreased N-acetylation activity toward caffeine metabolites (15558239, 17011540) and isoniazid (9154882, 28959610). Seven out of nine variant effect predictors tested by CPIC staff predict that c.590G>A (p.R197Q) impairs protein function. In vitro studies have shown that NAT2*34 exhibits decreased thermostability and decreased N-acetyltransferase activity toward sulfamethazine and isoniazid (28523442).	\N	f
6355214	9	CFTR	A120T	\N	ivacaftor responsive	\N	\N	6355213	{}	\N	\N	\N	\N	f
6355216	9	CFTR	A234D	\N	ivacaftor responsive	\N	\N	6355215	{}	\N	\N	\N	\N	f
6355272	9	CFTR	G576A	\N	ivacaftor responsive	\N	\N	6355271	{}	\N	\N	\N	\N	f
6355274	9	CFTR	G970D	\N	ivacaftor responsive	\N	\N	6355273	{}	\N	\N	\N	\N	f
778173	339	CYP2D6	*127	\N	Unknown function	\N	n/a	778172	{}	No Evidence	\N	CYP2D6*127 is assigned unknown function due to no literature describing function of this allele. Therefore, consensus among experts was unknown function due to no available evidence.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
6481197	6	NAT2	*6	Slow	Decreased function	\N	\N	6481196	{9154882,8781741,29589062,28653770,8102597,30564082,15558239,7668286,2376572,1451720,10744128,22092036,1872889,20040334,9333101,22970273,16531626,15565348,9321764,9110365,11214777,31257615,24702251,24444407,15110095,27509179,11773863,20801937,21750470,23899363,9565293,9891107,9682266,24221535,22105431,8287065,27223070,8001235,8923605,10762005,8081359,35928262,28752039,17505821,21946899,16570187,15032315,18167504,17434923,33815485,18680467,19336229,7669073,11337936,28516247}	Definitive	\N	NAT2*6 is assigned decreased function based on definitive evidence. The NAT gene nomenclature committee has historically assigned acetylation activity to alleles as either "rapid" or "slow", classifying the NAT2*6 allele as "slow" . Under the CPIC allele function terminology, slow acetylation alleles are categorized as "Decreased Function". NAT2*6 is characterized by the core SNVs c.590G>A (p.R197Q) and c.803G>A (p.R268K). c.803G>A defines NAT2*4, formerly considered the reference allele, which has repeatedly exhibited increased function in vivo and in vitro. The functional SNV c.590G>A (p.R197Q) has been studied for more than 25 years and has shown decreased N-acetylation activity in numerous clinical and in vitro studies using various substrates. Clinical studies have demonstrated that individuals homozygous for NAT2*6 or heterozygous for NAT2*6 in combination with another decreased function allele exhibit decreased acetylation activity toward caffeine metabolites (8102597, 7668286, 9891107, 10744128, 20801937, 22970273, 24221535, 28653770), isoniazid (2376572, 9154882, 9321764, 19336229, 35928262), sulphonamides (1872889, 15032315, 16570187, 18167504, 21946899), and dapsone (10762005). Individuals homozygous for NAT2*6 or heterozygous for NAT2*6 in combination with another decreased function allele exhibit increased hydralazine exposure (24702251, 31257615). Seven out of nine variant effect predictors tested by CPIC staff predict that c.590G>A (p.R197Q) impairs protein function. In vitro studies have shown that NAT2*6 exhibits decreased thermostability and decreased protein expression (11337936, 17434923, 8081359) as well as decreased acetylation toward various substrates (7669073, 33815485). Several studies indicate the existence of an ultra-slow acetylator phenotype in individuals homozygous for the NAT2*6 allele compared with other NAT2 decreased function alleles (29018032, 28653770, 24221535, 33815485, 7668286, 22970273, 28752039, 16570187, 28516247).	\N	f
778713	296	G6PD	A- 202A_376G	III/Deficient	III/Deficient	\N	\N	778712	{22293322,32387609,2572288}	strong	\N	Function assigned based on the WHO recommendations included in PMID 22293322. Additional in vitro (32387609) and the presence of this variant in G6PD deficient males (2572288) supports this classificaiton.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
6481237	6	NAT2	*40	Slow	Decreased function	\N	\N	6481236	{28959610,17434923,18680467,11337936}	Definitive	\N	NAT2*40 is assigned decreased function based on definitive evidence. NAT2*40 is characterized by the core SNV c.857G>A (p.G286E, defining NAT2*7) which exhibits decreased N-acetylation activity toward sulfamethazine, decreased thermostability, and decreased protein expression in a mammalian cell lines compared to NAT2*4 (17434923). NAT2*40 also exhibits decreased protein levels when expressed in yeast cells (11337936). A clinical NAT2 phenotyping studying using isoniazid (INH) as a probe drug identified 2 patients carrying NAT2*40 (28959610). These individuals were classified among slow acetylators, who exhibited an acetylation index (defined as the ratio of plasma INH concentration at the 3rd hour, in mg/L + 0.6 divided by the dose in mg/kg) below that of rapid acetylators, which were defined as individuals homozygous for NAT2 increased function alleles *1 or *4 (28959610). Nine out of nine variant effect predictors tested by CPIC staff predict that c.857G>A (p.G286E) does not impair protein function. However, published in silico modeling indicates that c.857G>A (p.G286E) disrupts the size/shape of the protein's active site (18680467).	\N	f
6481259	6	NAT2	*51	\N	Uncertain function	\N	\N	6481258	{26620671,29273096}	Inadequate	\N	NAT2*51 is assigned uncertain function based on inadequate evidence. There is no experimental evidence describing function for c.121A>T (p.N41Y). Seven out of nine variant effect predictors tested by CPIC staff predict that c.121A>T impairs protein function which agrees with published computational predictions indicating reduced function for c.121A>T (29273096).	\N	f
6355228	9	CFTR	D192G	\N	ivacaftor responsive	\N	\N	6355227	{}	\N	\N	\N	\N	f
6355232	9	CFTR	D924N	\N	ivacaftor responsive	\N	\N	6355231	{}	\N	\N	\N	\N	f
6355242	9	CFTR	E822K	\N	ivacaftor responsive	\N	\N	6355241	{}	\N	\N	\N	\N	f
6355246	9	CFTR	F311del	\N	ivacaftor responsive	\N	\N	6355245	{}	\N	\N	\N	\N	f
6355248	9	CFTR	F311L	\N	ivacaftor responsive	\N	\N	6355247	{}	\N	\N	\N	\N	f
6355250	9	CFTR	F508C	\N	ivacaftor responsive	\N	\N	6355249	{}	\N	\N	\N	\N	f
6355258	9	CFTR	G178E	\N	ivacaftor responsive	\N	\N	6355257	{}	\N	\N	\N	\N	f
6355262	9	CFTR	G194R(G>A)	\N	ivacaftor responsive	\N	\N	6355261	{}	\N	\N	\N	\N	f
6355264	9	CFTR	G194R(G>C)	\N	ivacaftor responsive	\N	\N	6355263	{}	\N	\N	\N	\N	f
6355266	9	CFTR	G314E	\N	ivacaftor responsive	\N	\N	6355265	{}	\N	\N	\N	\N	f
6481199	6	NAT2	*7	Slow	Decreased function	\N	\N	6481198	{9154882,29589062,28653770,8102597,30564082,15558239,7668286,2376572,10744128,22092036,1872889,8689813,20040334,17011540,16531626,9321764,9110365,11214777,31257615,15110095,27509179,11773863,16003747,21750470,9565293,9891107,9682266,8287065,27223070,8001235,8923605,10762005,8081359,35928262,17505821,21946899,16570187,15032315,18167504,17434923,33815485,18680467,19336229,7669073,20801937,22970273,24221535,11337936}	Definitive	\N	NAT2*7 is assigned decreased function based on definitive evidence. The NAT gene nomenclature committee has historically assigned acetylation activity to alleles as either "rapid" or "slow", classifying the NAT2*7 allele as "slow" and possibly substrate dependent. Under the CPIC allele function terminology, slow acetylation alleles are categorized as "Decreased Function". NAT2*7 is characterized by the core SNVs c.857G>A (p.G286E) and c.803G>A (p.R268K). c.803G>A defines NAT2*4, formerly considered the reference allele, which has repeatedly exhibited increased function in vivo and in vitro. The functional SNV c.857G>A (p.G286E) has been studied for more than 25 years and has shown decreased NAT2 N-acetylation activity in both clinical and in vitro studies using various substrates. Clinical studies have demonstrated that individuals homozygous for NAT2*7 or heterozygous for NAT2*7 in combination with another decreased function allele exhibit decreased acetylation activity toward caffeine metabolites (8102597, 7668286, 9891107, 10744128, 20801937, 22970273, 24221535, 28653770), isoniazid (2376572, 9154882, 9321764, 19336229, 35928262), and sulphonamides (1872889, 15032315, 16570187, 18167504, 21946899). Individuals homozygous for NAT2*7 or heterozygous for NAT2*7 in combination with another decreased function allele exhibit increased hydralazine exposure (24702251, 31257615). In vitro studies have shown that NAT2*7 has decreased N-acetylation activity toward numerous substrates (8081359, 7669073), and NAT2*7 exhibits substrate specificity , exhibiting increased affinity for diaminodiphenyl sulfone (dapsone), sulfamethazine, and sulfapyridine, and decreased affinity for its cofactor, acetyl-CoA as compared to the former reference NAT2*4 (17434923, 33815485, 7669073, 11337936). Nine out of nine variant effect predictors tested by CPIC staff predict that c.857G>A (p.G286E) does not impair protein function. Published in silico modeling predicts that c.857G>A disrupts the size/shape of the protein's active site (18680467), this result combined with the decreased affinity for acetyl-CoA is likely the molecular mechanism for the decreased acetylation activity observed.	\N	f
6481213	6	NAT2	*27	\N	Uncertain function	\N	\N	6481212	{19164093,29273096}	Inadequate	\N	NAT2*27 is assigned uncertain function based on inadequate evidence. NAT2*27 is characterized by the core SNVs c.589C>T and c.803G>A. c.803G>A defines NAT2*4, formerly considered the reference allele, which has repeatedly exhibited increased function in vivo and in vitro. c.589C>T results in the amino acid change p.R197X, introducing a premature stop codon leading to the expression of a truncated protein product that is predicted to be nonfunctional (19164093, 29273096). Four out of four variant effect predictors tested by CPIC staff predict that c.589C>T (p.R197X) impairs function. While in silico predictions indicate that NAT2*27 exhibits decreased or possibly no enzymatic activity, the committee could not come to a consensus given the lack of in vitro or in vivo data to support the function.	\N	f
6481277	6	NAT2	*60	\N	Unknown function	\N	\N	6481276	{}	No evidence	\N	NAT2*60 is assigned unknown function based on a lack of evidence. NAT2*60 is characterized by the core SNVs c.491T>C (p.I164T) and c.803G>A (p.R268K). c.803G>A (p.R268K) defines NAT2*4, formerly considered the reference allele, which has repeatedly shown increased function in vivo and in vitro. There is no literature describing function for c.491T>C (p.I164T). Nine out of nine variant effect predictors tested by CPIC staff predict that c.491T>C (p.I164T) is neutral for protein function	\N	f
777549	344	CYP2C19	*9	\N	Decreased function	\N	\N	777548	{12464799,21325430,25001882,21692664}	Limited	\N	CYP2C19*9 is assigned decreased function based on limited evidence. Three in vitro studies using different cell systems found CYP2C19*9 demonstrated decreased enzyme activity compared to wildtype with mephenytoin, omeprazole, and clopidogrel substrates (12464799, 21325430, 25001882). Another study found CYP2C19*9 exhibited significantly reduced catalytic activities compared with CYP2C19*1 across multiple substrates (21692664).Therefore, consensus among experts was decreased function based on limited evidence as it was determined the phenotypes containing this allele would be clinically distinct from phenotypes comprising normal function alleles.	{"Latino": 0.0008389262, "American": null, "European": 0.0006602626, "Oceanian": null, "East Asian": 0.00011504832, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": 0.026961539, "African American/Afro-Caribbean": 0.014347053}	f
778009	340	CYP2D6	*38	\N	No function	\N	0.0	778008	{9918137}	Limited	\N	CYP2D6*38 is assigned no function based on limited evidence in a heterozygous subject. CYP2D6*38 was identified in a heterozygous subject with CYP2D6 *4/*38 genotype demonstrating poor metabolism with a debrisoquine substrate (9918137). CYP2D6*38 is defined by a four base pair deletion resulting in a frameshift. Therefore, consensus among experts was no function with an activity value of 0 based on limited evidence as it was determined the phenotypes containing this allele would be clinically distinct from phenotypes comprising normal and decreased function alleles.	{"Latino": null, "American": null, "European": 0.0, "Oceanian": null, "East Asian": 0.0, "Near Eastern": 0.0, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778701	296	G6PD	Amsterdam	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778700	{22293322,12130518}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
778957	296	G6PD	Anadia	II/Deficient	II/Deficient	\N	\N	778956	{22293322,1945893,18056001}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
778961	296	G6PD	Clinic	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778960	{22293322,7825590}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
6481295	4	NAT2	*6J	\N	\N	\N	\N	6481294	\N	\N	\N	\N	\N	f
6481299	4	NAT2	*7G	\N	\N	\N	\N	6481298	\N	\N	\N	\N	\N	f
6481229	6	NAT2	*36	Slow	Decreased function	\N	\N	6481228	{}	Moderate	\N	NAT2*36 is assigned decreased function based on moderate evidence. NAT2*36 is characterized by the core SNVs c.403C>G (p.L135V), c.590G>A (p.R197Q), and c.803G>A (p.R268K). c.803G>A (p.R268K) defines NAT2*4, formerly considered the reference allele, which has repeatedly shown increased function in vivo and in vitro. There is no literature describing function for c.403C>G (p.L135V). Eight out of nine variant effect predictors tested by CPIC staff predict that c.403C>G is neutral/tolerated for protein function. c.590G>A (p.R197Q) defines NAT2*6 which has been extensively studied, exhibiting decreased N-acetyltransferase activity both in vivo and in vitro. Similarly, seven out of nine variant effect predictors tested by CPIC staff predict that c.590G>A impairs protein function. Thus, NAT2*36 is assigned decreased function based on c.590G>A. While c.403C>G is not predicted to impair protein function, it remains unknown whether there are any combinatorial effects associated with c.590G>A and c.403C>G.	\N	f
777551	344	CYP2C19	*10	\N	Decreased function	\N	\N	777550	{12464799,19661214,21325430,25001882,24945780,21692664}	Limited	\N	CYP2C19*10 is assigned decreased function based on limited evidence.Six in vitro studies using different cell systems found CYP2C19*10 demonstrated decreased enzyme activity compared to wildtype with mephenytoin, omeprazole, and clopidogrel substrates (12464799, 19661214, 21325430, 25001882, 24945780). Another study found CYP2C19*10 exhibited significantly reduced catalytic activities compared with CYP2C19*1 across multiple substrates (21692664). Therefore, consensus among experts was decreased function based on limited evidence as it was determined the phenotypes containing this allele would be clinically distinct from phenotypes comprising normal function alleles.	{"Latino": 0.0012398496, "American": null, "European": 0.0, "Oceanian": null, "East Asian": 0.00010471204, "Near Eastern": 0.0, "Central/South Asian": null, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.0032672414}	f
778145	339	CYP2D6	*113	\N	Uncertain function	\N	n/a	778144	{31368850}	Inadequate	\N	CYP2D6*113 is assigned uncertain function. CYP2D6*113 is defined by a SNP which in silico studies predict to be a deleterious amino acid change (31368850). Consensus was not achieved among experts as data were sparse. Therefore, uncertain function was assigned.	{"Latino": null, "American": 0.0, "European": 0.0, "Oceanian": null, "East Asian": 0.0, "Near Eastern": null, "Central/South Asian": 0.008, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.0}	f
6481243	6	NAT2	*43	\N	Uncertain function	\N	\N	6481242	{19909761,24444407}	Inadequate	\N	NAT2*43 is assigned uncertain function based on inadequate evidence. NAT2*43 is characterized by the core SNV c.609G>T (p.E203D). Published in silico modeling predicts that c.609G>T (p.E203D) does not alter NAT2 protein function (19909761). Similarly, eight out of nine variant effect predictors tested by CPIC staff predict that c.609G>T (p.E203D) is neutral/tolerated for NAT2 protein function. The limited clinical data available for NAT2*43 was not sufficient to influence the allele clinical functional status.(24444407).	\N	f
778175	339	CYP2D6	*128	\N	Uncertain function	\N	n/a	778174	{32759992}	Inadequate	\N	CYP2D6*128 is assigned uncertain function due to inadequate literature describing function of this allele. One in vitro study demonstrated substantially decreased intrinsic clearance CLint (Vmax/Km) of 3.3% compared to *1 for tamoxifen N-desmethylation (32759992); no activity was detectable for dextromethorphan O-demethylation. Therefore, consensus among experts was uncertain function due to inadequate evidence.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778482	325	DPYD	c.2978T>G	Normal function	Normal function	\N	1.0	778481	{24648345}	Limited	\N	5-fluorouracil (in vitro)	{"Latino": 0.0, "European": 0.0, "East Asian": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": 0.0019285714, "African American/Afro-Caribbean": 0.0}	f
6481245	6	NAT2	*44	\N	Uncertain function	\N	\N	6481244	{19909761,28959610,24444407}	Inadequate	\N	NAT2*44 is assigned uncertain function based on inadequate evidence. NAT2*44 is characterized by the core SNV c.403C>G (p.L135V). There is no experimental evidence describing function for c.403C>G (p.L135V). Published in silico modeling predicts that c.403C>G (p.L135V) does not alter NAT2 protein function (19909761). Similarly, eight out of nine variant effect predictors tested by CPIC staff predict that c.403C>G (p.L135V) is neutral/tolerated for NAT2 protein function. The limited clinical data available for NAT2*44 was not sufficient to influence the allele clinical functional status (24444407). Additionally, a NAT2 phenotyping study identified a patient with the genotype NAT2*5/*44, however this individual was excluded from phenotype analysis (28959610).	\N	f
777965	340	CYP2D6	*15	\N	No function	\N	0.0	777964	{8807669}	Limited	\N	CYP2D6*15 is assigned no function based on limited evidence. CYP2D6*15 was first described in a subject demonstrating markedly decreased dextromethorphan and debrisoquine metabolism (8807669). CYP2D6*15 is defined by an amino acid insertion resulting in missense sequence and premature stop codon, yielding a truncated nonfunctional enzyme. Therefore, consensus among experts was no function with an activity value of 0 based on limited evidence as it was determined the phenotypes containing this allele would be clinically distinct from phenotypes comprising normal and decreased function alleles.	{"Latino": 0.0, "American": 0.0009130435, "European": 0.0004858789, "Oceanian": 0.0, "East Asian": 0.00009106044, "Near Eastern": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": 0.0023071566, "African American/Afro-Caribbean": 0.0}	f
6481257	6	NAT2	*50	Slow	Decreased function	\N	\N	6481256	{}	Moderate	\N	NAT2*50 is assigned decreased function based on moderate evidence. NAT2*50 is characterized by the core SNVs c.7A>G (p.I3V), c.590G>A (p.R197Q), and c.803G>A (p.R268K). c.803G>A (p.R268K) defines NAT2*4, formerly considered the reference allele, which has repeatedly shown increased function in vivo and in vitro. There is no literature supporting a function for c.7A>G (p.I3V). One out of nine variant effect predictors tested by CPIC staff predicts that c.7A>G (p.I3V) impairs protein function. c.590G>A (p.R197Q) defines NAT2*6 which has repeatedly shown decreased N-acetyltransferase activity in numerous in vivo and in vitro studies. Similarly, seven out of nine variant effect predictors tested by CPIC staff predict that c.590G>A (p.R197Q) impairs protein function. Thus, NAT2*50 is assigned decreased function based on c.590G>A. While c.7A>G is not predicted to impair protein function, the combinatorial effects associated with c.590G>A and c.7A>G are uncertain.	\N	f
779003	296	G6PD	Andalus	II/Deficient	II/Deficient	\N	\N	779002	{22293322,12497642,32425388,16088936,2393028}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": 0.0, "European": 0.0, "East Asian": 0.00007233273, "Central/South Asian": 0.0, "African American/Afro-Caribbean": 0.0}	f
778709	296	G6PD	Asahi	III/Deficient	III/Deficient	\N	\N	778708	{22293322,32387609,11852882}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": 0.0041368, "European": 0.00016199434, "East Asian": 0.0, "Central/South Asian": 0.00036695323, "African American/Afro-Caribbean": 0.11640658}	f
778881	296	G6PD	Kalyan-Kerala, Jamnaga, Rohini	III/Deficient	III/Deficient	\N	\N	778880	{22293322,1303182,15996881}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": 0.0, "European": 0.00004499883, "East Asian": 0.0, "Central/South Asian": 0.011377339, "African American/Afro-Caribbean": 0.0}	f
3685343	135	RYR1	c.479A>G	Variant of uncertain significance	Uncertain function	\N	n/a	3685342	{35849058}	\N	\N	PS4_Sup, PM1, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
6481263	6	NAT2	*53	Slow	Decreased function	\N	\N	6481262	{}	Moderate	\N	NAT2*53 is assigned decreased function based on moderate evidence. NAT2*53 is characterized by the core SNVs c.248G>C (p.G83A), c.590G>A (p.R197Q) and c.803G>A (p.R268K). c.803G>A (p.R268K) defines NAT2*4, formerly considered the reference allele, which has repeatedly shown increased function in vivo and in vitro. There is no experimental evidence describing function for c.248G>C (p.G83A). Seven out of nine variant effect predictors tested by CPIC staff predict that c.248G>C (p.G83A) impairs protein function. Similarly, published in silico analysis indicates that c.248G>C (p.G83A) is deleterious for protein function (Abodlaa et al. 2019; Bilal et al. 2022). c.590G>A (p.R197Q) defines NAT2*6 which has been extensively studied, exhibiting decreased N-acetyltransferase activity both in vivo and in vitro. Similarly, seven out of nine variant effect predictors tested by CPIC staff predict that c.590G>A (p.R197Q) impairs protein function. Thus, NAT2*53 is assigned decreased function based on c.590G>A. Despite this, the combinatorial effects associated with c.248G>C and c.590G>A are uncertain.	\N	f
6481265	6	NAT2	*54	\N	Uncertain function	\N	\N	6481264	{19909761}	Inadequate	\N	NAT2*54 is assigned uncertain function based on inadequate evidence. NAT2*54 is characterized by the core SNVs c.29T>C (p.I10T) and c.803G>A (p.R268K). c.803G>A (p.R268K) defines NAT2*4, formerly considered the reference allele, which has repeatedly shown increased function in vivo and in vitro. Published in silico modeling predicts that c.29T>C (p.I10T) does not alter NAT2 protein function (19909761). However, five out of nine variant effect predictors tested by CPIC staff predict that c.29T>C (p.I10T) impairs NAT2 protein function. Additionally, a structure-based computational prediction tool predicts that c.29T>C (p.I10T) decreases NAT2 protein stability which could lead to decreased function.	\N	f
6481269	6	NAT2	*56	Slow	Decreased function	\N	\N	6481268	{}	Moderate	\N	NAT2*56 is assigned decreased function based on moderate evidence. NAT2*56 is characterized by the core SNVs c.58G>T (p.D20Y), c.590G>A (p.R197Q) and c.803G>A (p.R268K). c.803G>A (p.R268K) defines NAT2*4, formerly considered the reference allele, which has repeatedly shown increased function in vivo and in vitro. There is no literature describing function for c.58G>T (p.D20Y). Eight out of nine variant effect predictors tested by CPIC staff predict that c.58G>T (p.D20Y) impairs protein function. c.590G>A (p.R197Q) defines NAT2*6 which has been extensively studied, exhibiting decreased N-acetyltransferase activity both in vivo and in vitro. Similarly, seven out of nine variant effect predictors tested by CPIC staff predict that c.590G>A (p.R197Q) impairs protein function. Thus, NAT2*56 is assigned decreased function based on c.590G>A. Despite this, the combinatorial effects associated with c.58G>T and c.590G>A are uncertain.	\N	f
777683	344	CYP2C9	*8	Decreased function	Decreased function	\N	0.5	777682	{23752738,22378156,23959274,16220110,21811894,23844998,24118918,25142737,25144335,25476996,25832633,25884291,25924705,27163851,27199745,25951663,24077631,15289788,28758225,23376925,15284535}	Definitive	\N	CYP2C9*8 is assigned decreased function based on definitive evidence in heterozygous patients and in vitro studies. Ten CYP2C9*1/*8 genotype patients on a stable warfarin dose had 28% lower S-warfarin clearance compared to wildtype patients which correlated with the in vitro kinetic study demonstrating the CYP2C9*8 protein had 30% reduced warfarin clearance compared to wildtype (22378156). The CYP2C9*8 allele was associated with decreased phenytoin metabolism in 19 subjects (CYP2C9*1/*8, CYP2C9*8/*9, CYP2C9*8/*11, or CYP2C9*5/*8) compared to wildtype subjects based on urinary excretion of a phenytoin metabolite after a single 300mg dose (16220110). Four CYP2C9*1/*8 subjects had decreased diclofenac metabolism compared to wildtype subjects based on the urinary metabolite ratio after a single 50mg dose (23959274). One in vitro study showed CYP2C9*8 had decreased mRNA expression compared to wildtype, resulting in decreased function and metabolism of substrates (23376925). Decreased metabolism of multiple substrates compared to wildtype was demonstrated in a series of in vitro studies (23752738, 27199745, 23844998, 24118918, 25142737, 25144335, 25476996, 25832633, 25884291, 25924705, 27163851, 25951663, 24077631). Although an in vitro study showed similar diclofenac metabolism compared to wildtype (22378156), the experts did not find this conflicting because four CYP2C9*1/*8 subjects exhibited decreased diclofenac metabolism as previously described (23959274). Additionally, the experts did not deem two in vitro studies where CYP2C9*8 demonstrated similar to increased enzyme activity compared to wildtype (28758225, 15284535) as conflicting evidence because both studies used the same system, and it could not be ruled out that these results which differed from the majority of in vitro studies were due to the specific system. Although six CYP2C9*1/*8 subjects had similar acenocoumarol metabolite plasma concentrations compared to wildtype subjects 8 and 24 hours after a single 8mg dose (21811894), the experts did not deem this result as conflicting evidence based on the small sample size. Similarly, two CYP2C9 *1/*8 subjects had a similar urinary losartan-metabolite ratio compared to wildtype after a single 25mg dose and the experts did not deem this result as convincing conflicting evidence based on the small sample size (15289788). Therefore, consensus among experts was decreased function with an activity value of 0.5 based on definitive evidence.	{"Latino": 0.0073706377, "American": 0.020382864, "European": 0.0018053303, "Oceanian": null, "East Asian": 0.0037306643, "Near Eastern": 0.00064213155, "Central/South Asian": 0.0009815951, "Sub-Saharan African": 0.075846866, "African American/Afro-Caribbean": 0.059034664}	f
778492	325	DPYD	c.3067C>A	Normal function	Normal function	\N	1.0	778491	{23588312}	Limited	\N	5-fluorouracil (ex vivo)	{"Latino": 0.00089275226, "European": 0.000013283348, "East Asian": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": 0.034825396, "African American/Afro-Caribbean": 0.044617835}	f
6481271	6	NAT2	*57	\N	Unknown function	\N	\N	6481270	{}	No evidence	\N	NAT2*57 is assigned unknown function based on a lack of evidence. NAT2*57 is characterized by the core SNVs c.321C>A (p.H107Q) and c.803G>A (p.R268K). c.803G>A (p.R268K) defines NAT2*4, formerly considered the reference allele, which has repeatedly shown increased function in vivo and in vitro Eight out of nine variant effect predictors tested by CPIC staff predict that c.321C>A (p.H107Q) impairs protein function	\N	f
778733	296	G6PD	Vancouver	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778732	{22293322,1353664}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
3685559	135	RYR1	c.6599C>T	Variant of uncertain significance	Uncertain function	\N	n/a	3685558	{35849058}	\N	\N	PS4_Sup, PM1, PP1_Mod	{"Latino": null, "American": null, "European": 0.0000294, "East Asian": 0.0001931, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
778161	339	CYP2D6	*121	\N	Unknown function	\N	n/a	778160	{}	No Evidence	\N	CYP2D6*121 is assigned unknown function due to no literature describing function of this allele. Therefore, consensus among experts was unknown function due to no available evidence.	{"Latino": null, "American": 0.0, "European": 0.0, "Oceanian": null, "East Asian": 0.0, "Near Eastern": null, "Central/South Asian": 0.0, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.003}	f
778705	296	G6PD	Musashino	III/Deficient	III/Deficient	\N	\N	778704	{22293322,3591235}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
779169	323	RYR1	c.1201C>T	Pathogenic	Malignant Hyperthermia associated	\N	n/a	779168	{33767344}	\N	\N	PS3_Mod, PS4_Mod, PM1_Sup, PM5, PP1, PP3_Mod	{"Latino": null, "American": null, "European": 0.0000294, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": 0.00002414}	f
2091245	244	CYP2D6	*156	\N	No function	\N	0.0	2091244	{}	Limited	\N	CYP2D6*156 is assigned no function based on limited evidence. CYP2D6*156 is defined by the five SNPs defining the decreased function *29 allele and one additional SNP, 154C>T which causes a premature stop codon (Q52X) that likely renders the allele nonfunctional. Therefore, consensus among experts was no function.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": 0.00104, "African American/Afro-Caribbean": null}	f
778697	296	G6PD	Metaponto	III/Deficient	III/Deficient	\N	\N	778696	{22293322,2253938}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
778815	296	G6PD	Minnesota, Marion, Gastonia, LeJeune	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778814	{22293322,1999409,1805484}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": 0.0, "European": 0.00001025599, "East Asian": 0.0, "Central/South Asian": 0.0, "African American/Afro-Caribbean": 0.0}	f
778975	296	G6PD	Munich	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778974	{22293322,17637841}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": 0.000010226099, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
6481275	6	NAT2	*59	Slow	Decreased function	\N	\N	6481274	{18680467}	Moderate	\N	NAT2*59 is assigned decreased function based on moderate evidence. NAT2*59 is characterized by the core SNVs c.475T>A (p.W159R), c.803G>A (p.R268K), and c.857G>A (p.G286E). c.803G>A (p.R268K) defines NAT2*4, formerly considered the reference allele, which has repeatedly shown increased function in vivo and in vitro. There is no literature describing function for c.475T>A (p.W159R). Eight out of nine variant effect predictors tested by CPIC staff predict that c.475T>A (p.W159R) impairs protein function. c.857G>A (p.G286E) defines NAT2*7 which has been extensively studied, exhibiting decreased N-acetyltransferase activity both in vivo and in vitro. Nine out of nine variant effect predictors tested by CPIC staff predict that c.857G>A (p.G286E) does not impair protein function. However, published in silico modeling indicates that c.857G>A (p.G286E) disrupts the size/shape of the protein's active site (18680467). Thus, NAT2*59 is assigned decreased function based on c.857G>A. Despite this, the combinatorial effects associated with c.475T>A and c.857G>A are uncertain.	\N	f
6481279	6	NAT2	*61	\N	Unknown function	\N	\N	6481278	{}	No evidence	\N	NAT2*61 is assigned unknown function based on a lack of evidence. NAT2*61 is characterized by the core SNVs c.506A>G (p.Y169C) and c.803G>A (p.R268K). c.803G>A (p.R268K) defines NAT2*4, formerly considered the reference allele, which has repeatedly shown increased function in vivo and in vitro. There is no literature describing function for c.506A>G (p.Y169C). Four out of nine variant effect predictors tested by CPIC staff predict that c.506A>G (p.Y169C) impairs protein function.	\N	f
779015	296	G6PD	Nice	III/Deficient	III/Deficient	\N	\N	779014	{22293322,9233561}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
6481281	6	NAT2	*62	Slow	Decreased function	\N	\N	6481280	{}	Moderate	\N	NAT2*62 is assigned decreased function based on moderate evidence. NAT2*62 is characterized by the core SNVs c.536A>G (p.H179R), c.590G>A (p.R197Q) and c.803G>A (p.R268K). c.803G>A (p.R268K) defines NAT2*4, formerly considered the reference allele, which has repeatedly shown increased function in vivo and in vitro. There is no literature describing function for c.536A>G (p.H179R). Nine out of nine variant effect predictors tested by CPIC staff predict that c.536A>G (p.H179R) does not impair protein function. c.590G>A (p.R197Q) defines NAT2*6 which has been extensively studied, exhibiting decreased N-acetyltransferase activity both in vivo and in vitro. Similarly, seven out of nine variant effect predictors tested by CPIC staff predict that c.590G>A (p.R197Q) impairs protein function. Thus, NAT2*62 is assigned decreased function based on c.590G>A. Despite this, the combinatorial effects associated with c.536A>G and c.590G>A are uncertain	\N	f
6481283	6	NAT2	*63	Slow	Decreased function	\N	\N	6481282	{}	Moderate	\N	NAT2*63 is assigned decreased function based on moderate evidence. NAT2*63 is characterized by the core SNVs c.590G>A (p.R197Q), c.650T>A (p.F217Y) and c.803G>A (p.R268K). c.803G>A (p.R268K) defines NAT2*4, formerly considered the reference allele, which has repeatedly shown increased function in vivo and in vitro. There is no literature describing function for c.650T>A (p.F217Y). Seven out of nine variant effect predictors tested by CPIC staff predict c.650T>A (p.F217Y) impairs protein function. c.590G>A (p.R197Q) defines NAT2*6 which has been extensively studied, exhibiting decreased N-acetyltransferase activity both in vivo and in vitro. Similarly, seven out of nine variant effect predictors tested by CPIC staff predict that c.590G>A (p.R197Q) impairs protein function. Thus, NAT2*63 is assigned decreased function based on c.590G>A. Despite this, the combinatorial effects associated with c.650T>A and c.590G>A are uncertain.	\N	f
777451	344	CYP2B6	*15	Decreased or no function	Uncertain function	\N	\N	777450	{15190123,17559344,20517174,20662624,21746968,30201214}	Limited	\N	CYP2B6*15 (c.1172T>A, p.I391N) – Uncertain function: CYP2B6*15 is assigned uncertain function. In vitro studies using human liver microsomes (17559344, 15190123) and cDNA expression systems (15190123, 20517174, 21746968, 30201214) showed decreased to no enzyme activity for CYP2B6*15 compared to the *1 reference (20662624). However, due to the lack of any in vivo or clinical evidence, consensus among experts was uncertain function based on limited evidence.	{"Latino": 0.0016141976, "European": 0.0069231493, "Oceanian": null, "East Asian": 0.0, "Near Eastern": null, "Central/South Asian": 0.00009347988, "Sub-Saharan African": 0.014535101, "African American/Afro-Caribbean": 0.0}	f
2091259	244	CYP2D6	*163	\N	Unknown function	\N	n/a	2091258	{}	No Evidence	\N	CYP2D6*163 is assigned unknown function due to no literature describing function of this allele. CYP2D6*163 is defined by the two SNPs defining the normal function *2 allele and a SNP that is not found on any other star allele.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": 0.00052, "African American/Afro-Caribbean": null}	f
6481203	6	NAT2	*14	Slow	Decreased function	\N	\N	6481202	{8102597,9154882,28653770,7668286,22092036,9110365,24444407,21750470,9565293,24221535,10762005,8081359,17505821,21946899,17434923,18680467,11337936}	Definitive	\N	NAT2*14 is assigned decreased function based on definitive evidence. The NAT gene nomenclature committee has historically assigned acetylation activity to alleles as either "rapid" or "slow", classifying the NAT2*14 allele as "slow" . Under the CPIC allele function terminology, slow acetylation alleles are categorized as "Decreased Function". ". NAT2*14 is characterized by the core SNVs c.191G>A (p.R64Q) and c.803G>A (p.R268K). c.803G>A defines NAT2*4, formerly considered the reference allele, which has repeatedly exhibited increased function in vivo and in vitro. The functional SNV c.191G>A (p.R64Q) has been studied for more than 25 years and has shown decreased NAT2 N-acetylation activity in both clinical and in vitro studies using various substrates. Clinical studies demonstrate that individuals homozygous for NAT2*14 or heterozygous for NAT2*14 in combination with another decreased function allele exhibit decreased acetylation activity toward caffeine metabolites (8102597, 7668286, 9110365, 9565293, 21750470, 24221535, 28653770), isoniazid (9154882, 17505821), sulfamethazine (21946899), and dapsone (10762005). Six out of nine variant effect predictors tested by CPIC staff predict that c.191G>A (p.R64Q) impairs protein function. Published in silico modeling predicts that c.191G>A decreases protein stability and hinders electrostatic interactions (18680467). In vitro studies have demonstrated that NAT2*14 exhibits decreased protein expression and thermostability compared to the former reference, NAT2*4 (11337936, 17434923, 8081359).	\N	f
778095	340	CYP2D6	*88	\N	Uncertain function	\N	n/a	778094	{25469868,26310775,26666748,26544071,26406933,27109434,27097346,27016952,26542054,26937172,26968424,27203132,27251229,27354764,27538917}	Inadequate	\N	CYP2D6*88 is assigned uncertain function due to inadequate evidence. In vitro studies found CYP2D6*88 demonstrated enzyme activity ranging from similar to decreased activity compared to wildtype with various substrates (25469868, 26310775, 26666748, 26544071, 26406933, 27109434, 27097346, 27016952, 26542054, 26937172, 26968424, 27203132, 27251229, 27354764, 27538917). Therefore, consensus among experts was uncertain function.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
3685359	135	RYR1	c.528G>T	Variant of uncertain significance	Uncertain function	\N	n/a	3685358	{35849058}	\N	\N	PS4_Mod, PM1	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
6481215	6	NAT2	*29	Slow	Decreased function	\N	\N	6481214	{10762005,28523442,15564878}	Moderate	\N	NAT2*29 is assigned decreased function based on moderate evidence. The NAT gene nomenclature committee has historically assigned acetylation activity to alleles as either "rapid" or "slow", classifying the NAT2*29 allele as "slow" . Under the CPIC allele function terminology, slow acetylation alleles are categorized as "Decreased Function". NAT2*29 is characterized by the functional SNVs c.191G>A (p.R64Q, defining NAT2*14) and c.341T>C (p.I114T, defining NAT2*5) which have both repeatedly shown decreased NAT2 N-acetylation in numerous in vivo and in vitro studies. A NAT2 phenotyping study showed that an individual genotyped as NAT2*14/*29 exhibited decreased acetylation of dapsone, with values below the cut-off value used to discriminate phenotypic rapid from slow acetylators (10762005). An in vitro study using a bacterial expression system found that NAT2*29 exhibits decreased thermostability and decreased N-acetyltransferase activity toward sulfamethazine and isoniazid (28523442 ). An additional in vitro study showed that NAT2*5 (which contains the core SNV c.341T>C, p.I114T) is subjected to enhanced protein degradation by the proteasome (15564878). Thus, NAT2*29 would presumably be degraded in the same manner. Additionally, five and six out of nine variant effect predictors tested by CPIC staff predict that c.341T>C (p.I114T) and c.191G>A (p.R64Q) impair protein function, respectively. While c.191G>A and c.341T>C are both definitively attributed to decreased function individually, the combinatorial effects of having both variants present in the same allele are uncertain.	\N	f
6481217	6	NAT2	*30	Slow	Decreased function	\N	\N	6481216	{15558239,15564878}	Moderate	\N	NAT2*30 is assigned decreased function based on moderate evidence. The NAT gene nomenclature committee has historically assigned acetylation activity to alleles as either "rapid" or "slow", classifying the NAT2*30 allele as "slow" . Under the CPIC allele function terminology, slow acetylation alleles are categorized as "Decreased Function". NAT2*30 is characterized by the core SNVs: c.341T>C (p.I114T), 590G>A (p.R197Q), and c.803G>A (p.R268K). c.803G>A defines NAT2*4, formerly considered the reference allele, which has repeatedly exhibited increased function in vivo and in vitro. c.341T>C (defining NAT2*5) and c.590G>A (defining NAT2*6) have both repeatedly shown decreased NAT2 N-acetylation in numerous in vivo and in vitro studies. NAT2*30 was reported in a clinical NAT2 phenotyping study using caffeine as a probe drug; 4 individuals heterozygous for NAT2*30 exhibited decreased acetylation of caffeine metabolites (15558239 ). An additional in vitro study showed that NAT2*5 (which contains the core SNV c.341T>C, p.I114T) is subjected to enhanced protein degradation by the proteasome (15564878). Thus, NAT2*30 would presumably be degraded in the same manner. Five and seven out of nine variant effect predictors tested by CPIC staff predict that c.341T>C (p.I114T) and c.590G>A (p.R197Q) impair protein function, respectively, while eight out of eight predictors tested by CPIC staff predict that c.803G>A (p.R268K) is neutral/tolerated for protein function. Though c.341T>C and:c.590G>A are both definitively attributed to decreased function individually, the combinatorial effects of having both variants present in the same allele are uncertain.	\N	f
777547	344	CYP2C19	*8	\N	No function	\N	\N	777546	{10411572,21325430,25001882,21692664}	Limited	\N	CYP2C19*8 is assigned no function based on limited evidence in a heterozygous subject and in vitro studies. CYP2C19*8 was first described in a subject demonstrating decreased metabolism of mephenytoin based on urine metabolite concentrations. This correlated with an in vitro study which found CYP2C19*8 had decreased enzyme activity compared to wildtype with mephenytoin and tolbutamide substrates (10411572). Two additional in vitro studies using different cell systems found CYP2C19*8 had nondetectable enzyme activity with mephenytoin, omeprazole, and clopidogrel substrates (21325430, 25001882). Another study found CYP2C19*8 exhibited significantly reduced catalytic activities compared with CYP2C19*1 across multiple substrates and distinct function from other decreased function alleles (21692664). Therefore, consensus among experts was no function based on limited evidence as it was determined the phenotypes containing this allele would be clinically distinct from phenotypes comprising normal function and decreased function alleles.	{"Latino": 0.0012738854, "American": 0.0, "European": 0.0033593778, "Oceanian": null, "East Asian": 0.0, "Near Eastern": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.0011203007}	f
6481221	6	NAT2	*32	Slow	Decreased function	\N	\N	6481220	{1559981,9173883,19909761,15564878}	Moderate	\N	NAT2*32 is assigned decreased function based on moderate evidence. NAT2*32 is characterized by the core SNVs c.203G>A (p.C68Y) and c.341T>C (p.I114T). An in vitro study showed that substituting a glycine in place of cysteine at position p.68 abolished NAT2 N-acetyltransferase activity toward sulfamethazine, procainamide, p-aminosalicylic acid, and 2-aminofluorene; the authors discuss the high probability that p.Cys68 lies within the NAT2 active site and is directly involved in acetyl transfer (1559981). An additional in vitro study found that NAT2 p.C68A exhibited undetectable N-acetyltransferase activity toward p-aminosalicylic acid and sulfamethazine (9173883). Thus, substitution of a tyrosine in place of cysteine at residue p.68 would likely abolish NAT2 enzymatic activity. Published in silico modeling predicts that c.203G>A (p.C68Y) alters the NAT2 catalytic mechanism, rendering the protein non-functional (19909761). Lastly, eight out of nine variant effect predictors tested by CPIC staff predict that c.203G>A (p.C68Y) impairs protein function. c.341T>C (p.I114T) defines NAT2*5, which has repeatedly shown decreased NAT2 acetylation activity in numerous in vivo and in vitro studies. Additionally, an in vitro study showed that NAT2*5 is subjected to enhanced protein degradation by the proteasome (15564878). Thus, NAT2*32 would presumably be degraded in the same manner. While the committee agreed to the assignment of decreased function based on the function of c.341T>C (p.I114T), there was a lack of consensus regarding the function of c.203G>A (p.C68Y). It remains unknown whether there are any combinatorial effects associated with c.341T>C and c.203G>A.	\N	f
6481231	6	NAT2	*37	Slow	Decreased function	\N	\N	6481230	{29273096}	Moderate	\N	NAT2*37 is assigned decreased function based on moderate evidence. NAT2*37 is characterized by the core SNVs c.590G>A (p.R197Q), c.638C>T (p.P213L) and c.803G>A. c.803G>A (p.R268K) defines NAT2*4, formerly considered the reference allele, which has repeatedly shown increased function in vivo and in vitro. There is no experimental evidence describing function for c.638C>T (p.P213L). Seven out of nine variant effect predictors tested by CPIC staff predict that c.638C>T (p.P213L) impairs protein function, which is supported by published in silico analysis (29273096). c.590G>A (p.R197Q) defines NAT2*6 which has been extensively studied, exhibiting decreased N-acetyltransferase activity both in vivo and in vitro. Similarly, seven out of nine variant effect predictors tested by CPIC staff predict that c.590G>A impairs protein function. Thus, NAT2*37 is assigned decreased function based on c.590G>A. Despite this, it remains unknown whether there are any combinatorial effects associated with c.638C>T and c.590G>A.	\N	f
777939	340	CYP2D6	*2	\N	Normal function	\N	1.0	777938	{7903454,11037799,11266079,12915955,18784265,20456744,24647041,25469868,26310775,26542054,26652007,26937172,26968424,27203132,27251229,27354764,27538917,30366777}	Moderate	\N	CYP2D6*2 is assigned normal function based on moderate evidence. CYP2D6*2 has consistently been described in subjects demonstrating similar metabolism with various CYP2D6 substrates compared to wildtype (7903454, 11037799, 12915955, 20456744). Although in vitro studies found CYP2D6*2 had enzyme activity ranging from similar to decreased activity compared to wildtype, the in vitro data was not convincing as the differences in results may be due to differences in the expression system used (11266079, 18784265, 24647041, 25469868, 26310775, 26542054, 26652007, 26937172, 26968424, 27203132, 27251229, 27354764, 27538917, 30366777). Therefore, consensus among experts was normal function with an activity value of 1 based on moderate evidence.	{"Latino": 0.22684056, "American": 0.217449, "European": 0.18536054, "Oceanian": 0.0611197, "East Asian": 0.1191732, "Near Eastern": 0.19004925, "Central/South Asian": 0.27445427, "Sub-Saharan African": 0.1738963, "African American/Afro-Caribbean": 0.15468602}	f
778362	331	DPYD	c.868A>G	Decreased function	Decreased function	\N	0.5	778361	{24648345}	Limited	\N	5-fluorouracil (in vitro)	{"Latino": 0.00033666822, "European": 0.0, "East Asian": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": 0.002017857, "African American/Afro-Caribbean": 0.0}	f
778364	331	DPYD	c.929T>C	Normal function	Normal function	\N	1.0	778363	{24648345}	Limited	\N	5-fluorouracil (in vitro)	{"Latino": 0.0, "European": 0.000013648342, "East Asian": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778743	296	G6PD	Acrokorinthos	II/Deficient	II/Deficient	\N	\N	778742	{22293322,32387609,15223006,2393028}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null, "African American/Afro-Caribbean": null}	f
779181	323	RYR1	c.1654C>T	Likely Pathogenic	Malignant Hyperthermia associated	\N	n/a	779180	{33767344}	\N	\N	PS3_Mod, PS4_Mod, PM1, PP1	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685453	135	RYR1	c.2050G>C	Variant of uncertain significance	Uncertain function	\N	n/a	3685452	{35849058}	\N	\N	PS4_Sup, PP3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
779703	282	CYP2D6	*9x2	\N	Decreased function	\N	0.5	777952	{1844820,8101460,11266079,24647041,30366777}	Limited	\N	CYP2D6*9x2 is assigned decreased function based on limited evidence. CYP2D6*9 is assigned decreased function based on decreased protein expression and enzyme activity (1844820, 8101460, 11266079, 24647041, 30366777). Therefore, consensus among experts was decreased function with an activity value of 0.5 based on limited evidence as it was determined the phenotypes containing a duplication of this allele would demonstrate greater protein expression and enzyme activity than that of the nonduplicated allele and be clinically similar to phenotypes comprising decreased function alleles.	{"Latino": 0.0, "American": 0.0, "European": 0.000111773355, "Oceanian": null, "East Asian": 0.0, "Near Eastern": null, "Central/South Asian": 0.0, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.0}	f
778031	340	CYP2D6	*49	\N	Decreased function	\N	0.5	778030	{19158312,18784265,19364831,24647041,30366777}	Limited	\N	CYP2D6*49 is assigned decreased function based on limited evidence. Subjects with CYP2D6 *1/*49 genotypes demonstrated decreased dextromethorphan metabolism compared to wildtype subjects and subjects with CYP2D6 *10/*49 genotype demonstrated decreased dextromethorphan metabolism compared to subjects with CYP2D6 *1/*10 genotype (19364831). Multiple in vitro studies found CYP2D6*49 had decreased enzyme activity compared to wildtype with multiple substrates (18784265, 19158312, 24647041, 30366777). Therefore, consensus among experts was decreased function with an activity value of 0.5 based on limited evidence.	{"Latino": null, "American": 0.0, "European": 0.0, "Oceanian": null, "East Asian": 0.009911487, "Near Eastern": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.0}	f
778207	246	CYP2D6	*144	\N	No function	\N	0.0	778206	{33998274}	Limited	\N	CYP2D6*144 is assigned no function based on limited evidence. CYP2D6*144 is defined by a splice accepter variant predicting abberant splicing. A subject sequenced as CYP2D6*143/*144 had a risperidone/9-hydroxy-risperidone ratio that was higher (indicating lower activity) compared to that found in subjects with two no function alleles. Two subjects genotyped as *1/*144 and *2/*144 had ratios comparable to that of subjects with an AS of 1 (33998274). Therefore, consensus among experts was no function.	{"Latino": null, "American": 0.0, "European": 0.0, "Oceanian": null, "East Asian": 0.001, "Near Eastern": null, "Central/South Asian": 0.0, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.0}	f
