--
--

\restrict W4MDyxXge2cmt2KjTdm6PCggicmUwiig7hX2Sv1FDgYUdXfbmGWxPKpv2OQ7aac


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,
    clinpgxid 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.clinpgxid; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.drug.clinpgxid IS 'The ClinPGx 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,
    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.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 text NOT NULL,
    clinpgxlevel character varying(5),
    pgxtesting text,
    citations text[],
    removed boolean DEFAULT false,
    removeddate date,
    removedreason text,
    CONSTRAINT valid_cpiclevel_check CHECK ((cpiclevel = 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, ('Retired'::character varying)::text]))),
    CONSTRAINT valid_pgkblevel_check CHECK (((clinpgxlevel)::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.clinpgxlevel; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.pair.clinpgxlevel 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,
    clinpgxid 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 ((clinpgxid ~ '^(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.clinpgxid; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.gene.clinpgxid IS 'The ID for this gene in ClinPGx';


--
-- 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.clinpgxlevel,
    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.clinpgxlevel; Type: COMMENT; Schema: cpic; Owner: -
--

COMMENT ON COLUMN cpic.pair_view.clinpgxlevel IS 'The top level of ClinPGx Summary 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 ClinPGx 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;
1508727	376	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
3318590	139	CYP4F2	*10	\N	\N	\N	\N	3318589	\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
3318592	139	CYP4F2	*11	\N	\N	\N	\N	3318591	\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
779159	373	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
3685403	185	RYR1	c.1201C>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685402	{35849058}	\N	\N	PS4_Sup, PM1_Sup, PM5	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685491	185	RYR1	c.4178A>G	Benign	Normal function	\N	n/a	3685490	{35849058}	\N	\N	BA1	{"Latino": 0.001703, "American": null, "European": 0.0043866965, "East Asian": null, "Near Eastern": 0.0002882, "Central/South Asian": null, "Sub-Saharan African": 0.001086}	f
3685609	185	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
3685681	185	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
3685705	185	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
3685809	185	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
3685869	185	RYR1	c.12884C>T	Benign	Normal function	\N	n/a	3685868	{33767344}	\N	\N	BS1, BS2_Mod, BP2, BP4	{"Latino": 0.0006122, "American": null, "European": 0.0030186172, "East Asian": 0.0009812, "Near Eastern": 0.0002953, "Central/South Asian": null, "Sub-Saharan African": 0.00136}	f
3685905	185	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
779237	373	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
777328	240	CFTR	D1270N	\N	ivacaftor responsive	\N	\N	777327	{}	\N	\N	\N	\N	f
777569	394	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
1777304	296	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
779039	346	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
779284	372	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
779308	372	SLCO1B1	*16	\N	Uncertain function	\N	\N	779307	{12811365,33658230}	Inadequate	\N	SLCO1B1*16 is assigned uncertain function based on limited in vitro evidence and clinical data. One clinical study showed 2 heterozygous subjects treated with pravastatin had similar pharmacokinetic parameters to subjects with wildtype alleles and one invitro study found normal protein expression (33658230). Therefore, consensus among experts was uncertain function due to inadequate evidence.	{"American": null, "European": 0.0005718263, "Oceanian": null, "East Asian": 0.0045032115, "Near Eastern": null, "Central/South Asian": 0.0, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
779328	372	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
779344	372	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
1002696	366	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
777376	240	CFTR	S1255P	\N	ivacaftor responsive	\N	\N	777375	{}	\N	\N	\N	\N	f
777378	240	CFTR	S549N	\N	ivacaftor responsive	\N	\N	777377	{}	\N	\N	\N	\N	f
777382	240	CFTR	S549R(T>G)	\N	ivacaftor responsive	\N	\N	777381	{}	\N	\N	\N	\N	f
777384	240	CFTR	S945L	\N	ivacaftor responsive	\N	\N	777383	{}	\N	\N	\N	\N	f
777386	240	CFTR	S977F	\N	ivacaftor responsive	\N	\N	777385	{}	\N	\N	\N	\N	f
6355396	39	CFTR	T1053I	\N	ivacaftor responsive	\N	\N	6355395	{}	\N	\N	\N	\N	f
6355394	39	CFTR	T338I	\N	ivacaftor responsive	\N	\N	6355393	{}	\N	\N	\N	\N	f
6355398	39	CFTR	V232D	\N	ivacaftor responsive	\N	\N	6355397	{}	\N	\N	\N	\N	f
6355400	39	CFTR	V562I	\N	ivacaftor responsive	\N	\N	6355399	{}	\N	\N	\N	\N	f
6355402	39	CFTR	V754M	\N	ivacaftor responsive	\N	\N	6355401	{}	\N	\N	\N	\N	f
777699	394	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
778851	346	G6PD	Wexham	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778850	{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
3685375	185	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
3685499	185	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
779395	372	TPMT	*2	\N	No function	\N	\N	779394	{7862671,16220112,9177237,18708949,9246020,15226673,23252716,31005613,12880540,19057372,14508387,9695718,14656901,9103127,11372592,18021342,10580024,9831928,14985890}	Definitive	\N	TPMT*2 is assigned no function based on definitive evidence. Erythrocytes from individuals heterozygous for TPMT*2 exhibited intermediate enzymatic activity, while erythrocytes from individuals homozygous for TPMT*2 or heterozygous for TPMT*2 in combination with another no function allele exhibited low enzymatic activity (7862671, 9246020, 9695718, 15226673, 23252716, 31005613, 12880540, 14508387, 14656901, 9103127, 11372592, 18021342, 9831928, 14985890). Patients carrying TPMT*2 alleles exhibited increased plasma concentrations of TGNs, decreased plasma concentrations of methylated metabolites, and tolerated lower doses of thiopurines (19057372, 18021342, 10580024). In vitro studies found that TPMT.2 protein expression and enzymatic activity was decreased by 75-100% relative to TPMT*1 in yeast (7862671, 9177237) and mammalian cells (16220112, 9177237, 18708949), as well as patient erythrocytes (9177237, 9695718). TPMT.2 decreased protein expression has been attributed to rapid degradation by the proteasome (9177237, 16220112). Ten out of ten variant effect predictors tested by CPIC staff predict that the TPMT*2-defining SNV, c.238G>C (p.A80P), impairs protein function.	{"Latino": 0.0034579393, "European": 0.0020584913, "East Asian": 0.00008490133, "Near Eastern": 0.007194246, "Central/South Asian": 0.00022537795, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.0053066667}	f
779405	372	TPMT	*5	\N	No function	\N	\N	779404	{9246020,16220112,18708949}	Limited	\N	TPMT*5 is assigned no function based on limited evidence. Erythrocytes from an individual genotyped TPMT*1/*5 exhibited intermediate enzymatic activity (9246020). In vitro studies using mammalian cell expression systems found that TPMT.5 protein expression is decreased and TPMT.5 is degraded more rapidly compared to TPMT.1 (16220112). Additionally, TPMT.5 enzymatic activity is undetectable in vitro (16220112, 18708949). Nine out of ten variant effect predictors tested by CPIC staff predict that the TPMT*5-defining SNV, c.146T>C (p.L49S), impairs protein function.	{"Latino": null, "European": 0.0, "East Asian": 0.0, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
779417	372	TPMT	*11	\N	No function	\N	\N	779416	{18708949,12835738,16220112}	Limited	\N	TPMT*11 is assigned no function based on limited evidence. Erythrocytes from a patient genotyped TPMT*3A/*11 exhibited very low enzymatic activity and 6-MMP was undetectable in the patient's plasma and their 6-MP dose was reduced to 15% of the standard dosage (12835738). In vitro studies using mammalian cell expression systems found TPMT.11 protein expression is decreased (16220112). TPMT.11 enzymatic activity is decreased up to 97% in vitro and TPMT.11 exhibied decreased affinity for 6-MP, 6-TG, and SAM relative to TPMT.1 (16220112, 18708949). Seven out of ten variant effect predictors tested by CPIC staff predict that the TPMT*11-defining SNV, c.395G>A (p.C132Y), impairs protein function.	{"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
777953	390	CYP2D6	*9	\N	Decreased function	\N	0.25	777952	{1844820,8101460,11266079,24647041,30366777,32599653,33932135,33792048,33967790,30312494}	Moderate	\N	CYP2D6*9 is assigned decreased function based on moderate evidence. CYP2D6*9 was first identified in a liver sample with decreased protein expression and enzyme activity (1844820). Subjects with CYP2D6*9 demonstrated decreased debrisoquine metabolism but greater metabolism compared to subjects with no function alleles based on urine metabolites, indicating there is not a complete loss of enzyme function (8101460). Similarly, liver microsomes of two subjects with CYP2D6*4/*9 and CYP2D6 *1/*9 genotype demonstrated decreased intrinsic clearance compared to wildtype with a bufuralol substrate (11266079). Two in vitro studies found CYP2D6*9 had a modest decrease in intrinsic clearance compared to wildtype (24647041, 30366777). Although one in vitro experiment found CYP2D6*9 had similar activity compared to wildtype with various substrates, the result was not convincing as decreased protein expression in vivo likely contributes to decreased enzyme activity observed in subjects carrying the CYP2D6*9 allele (1844820). Pharmacogenomic clinical studies found the measured activity values for several substrates is reduced (0.34 (PMID 30312494), 0.18 (PMID 33792048), 0.28 (PMID 33792048), 0.22 (PMID 32599653); 0.46 PMID 33932135) and a lower activity value of 0.25 is warranted for most substrates. Therefore, consensus among experts was decreased function with an activity value of 0.25 based on moderate evidence.	{"Latino": 0.015500509, "American": 0.007059503, "European": 0.02754178, "Oceanian": 0.0, "East Asian": 0.0017375742, "Near Eastern": 0.0038028897, "Central/South Asian": 0.0018789063, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.0043313783}	f
778003	390	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
779732	323	CYP2D6	*35x2	\N	Increased function	\N	2.0	778002	{9511177}	Limited	\N	CYP2D6*35x2 is assigned increased function based on limited evidence in heterozygous subjects. CYP2D6*35x2 was described in a subject with CYP2D6*1/*35x2 genotype demonstrating increased enzyme activity with the greatest sparteine metabolism among 195 subjects based on urine metabolites. Additionally, a subject with CYP2D6 *5/*35x2 genotype demonstrated similar sparteine metabolism compared to wildtype subjects indicating increased enzyme activity (9511177). 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": 0.00093648373, "American": 0.00020282187, "European": 0.00057484733, "Oceanian": null, "East Asian": 0.0, "Near Eastern": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.00009041316}	f
778177	390	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
778424	375	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
779437	372	TPMT	*21	\N	No function	\N	\N	779436	{18708949,18602085,16917910,23252716,33118454}	Moderate	\N	TPMT*21 is assigned no function based on moderate evidence. Erythrocytes from individuals genotyped TPMT*1/*21 exhibited intermediate activity (18602085, 16917910, 23252716). Additionally, a patient genotyped TPMT*1/*21 was prescribed 41 mg/m2 thioguanine and exhibited a plasma TGN concentration of 4060 pmol, which is above the therapeutic range (23252716). Erythrocytes from an individual genotyped TPMT*3A/*21 had undetectable enzymatic activity (33118454). An in vitro study using a mammalian cell expression system found that TPMT.21 enzymatic activity was undetectable (18708949). An additional in vitro study using a yeast expression system found that TPMT.21 enzymatic activity is decreased by 75% compared to TPMT.1 and molecular modeling suggests that TPMT.21 alters the co-factor binding site (18602085). Seven out of ten variant effect predictors tested by CPIC staff predict that the TPMT*21-defining SNV, c.205C>G (p.L69V), impairs protein function.	{"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
778739	346	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
110055	147	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
3827877	167	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
3827917	167	MT-RNR1	m.1555A>G	Conformational change to the mitochondrial 12s rRNA leading to binding of aminoglycoside antibiotics	increased risk of aminoglycoside-induced hearing loss	\N	\N	3827916	{7689389,8285309,8414970,9039999,9040738,9111378,9164619,9391883,9490575,9779807,9831149,9950117,10633132,10661905,11174959,11857751,11870684,12031626,12920080,14699607,14755216,15708009,15841390,15917167,16168391,16375862,16458854,16935512,16955413,17341440,17637808,17723226,17999439,18386806,18790089,18820594,18830133,19376484,19818876,19835846,20100600,20111055,20353758,21162657,21205314,21504270,22475488,23256547,24252789,25744662,26497601,27397648,27427311,29805548,24703164,25155176,8687424,9315872,12127547,19687236,28103015,10915767,12054632,21828074}	Definitive	\N	MT-RNR1 1555A>G is assigned an increased risk of aminoglycoside-induced hearing loss based on definitive evidence. Screening of individuals or probands of individuals with aminoglycoside-hearing loss identified 1494C>T in a number of cases (7689389, 8285309, 8414970, 9039999, 9040738, 9111378, 9164619, 9391883, 9490575, 9779807, 9831149, 9950117, 10633132, 10661905, 11174959, 11857751, 11870684, 12031626, 12920080, 14699607, 14755216, 15708009, 15841390, 15917167, 16168391, 16375862, 16458854, 16935512, 16955413, 17341440, 17637808, 17723226, 17999439, 18386806, 18790089, 18820594, 18830133, 19376484, 19818876, 19835846, 20100600, 20111055, 20353758, 21162657, 21205314, 21504270, 22475488, 23256547, 24252789, 25744662, 26497601, 27397648, 27427311, 29805548, 24703164, 25155176). There is inhibiton of translation in fibroblasts and cybrid cell lines with 1555A>G mutation (8687424). Aminoglycosides bind to 12S rRNA carrying the G allele, but not to rRNA with the A allele (9315872, 12127547, 19687236, 28103015). LCLs with the 1555A>G mutation have reduced growth and translation when grown in paromomycin (10915767). No effect of 1555A>G mutation in fibroblast lines. Cybrids with 1555A>G had slower growth in neomycin or paromomycin (12054632, 21828074). Therefore, consensus among experts was this variant is associated with increased risk of aminoglycoside-induced hearing loss based on definitive evidence.	{"European": 0.0011348277, "East Asian": 0.018102558, "Near Eastern": 0.0014195286, "Central/South Asian": 0.0011089911, "Sub-Saharan African": 0.0030045942}	f
3685485	185	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
3685551	185	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
779439	372	TPMT	*22	\N	No function	\N	\N	779438	{18708949,16917910}	Limited	\N	TPMT*22 is assigned no function based on limited evidence. Erythrocytes from an individual genotyped TPMT*1/*22 exhibited intermediate activity (16917910). An in vitro study using a mammalian cell expression system found that TPMT.22 protein expression and enzymatic activity was undetectable (18708949). Ten out of ten variant effect predictors tested by CPIC staff predict that the TPMT*22-defining SNV, c.488G>C (p.R163P), impairs protein function.	{"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
779393	372	TPMT	*1	\N	Normal function	\N	\N	779392	{8561894,9177237,13679074,16220112,18708949,9246020,15226673,23252716,31005613,23585236,29387964,33928426,27564568,11304783,10580024,19057372}	Definitive	\N	TPMT*1 is assigned normal function based on definitive evidence. TPMT*1 corresponds to the reference sequence, NG_008807.2, containing no SNVs. As such, TPMT.1 activity is used as the reference for in vitro studies using yeast and mammalian cell expression systems (8561894, 9177237, 13679074, 16220112, 18708949). Erythrocytes from individuals genotyped TPMT*1/*1 exhibited normal to high enzymatic activity (9246020, 15226673, 23252716, 31005613). Lastly, TPMT*1/*1 patients have been shown to tolerate standard thiopurine dosing (23585236, 29387964, 33928426, 27564568, 11304783, 10580024, 19057372).	{"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
778085	389	CYP2D6	*83	\N	Uncertain function	\N	n/a	778084	{22111604}	Inadequate	\N	CYP2D6*83 is assigned uncertain function due to inadequate evidence. CYP2D6*83 is a rare hybrid allele associated with a CYP2D6*1 gene duplication (22111604). 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
778428	375	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
778895	346	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
779065	374	NUDT15	*1	\N	Normal function	\N	\N	779064	{26878724,28659275,27530327,32094176,34636169,38246006,31645647,37488179,27604507,34480209,35067667,28445187,32372428,33481917,32598049,28903549,32308129,29720126,36858569,35156873,32221476,31507415,27577869,27416873,26033531,32873882,39688234}	Definitive	\N	NUDT15*1 is assigned normal function based on definitive evidence. NUDT15*1 corresponds to the reference sequence, NG_047021.1, containing no SNVs. As such, the protein encoded by this transcript is used as the reference for in vitro (26878724, 28659275, 27530327, 32094176, 34636169, 38246006, preclinical (31645647, 37488179), and clinical studies (27604507, 26878724, 34480209, 35067667, 28445187, 32372428, 33481917, 39688234). Additionally, NUDT15*1/*1 patients have been shown to tolerate standard thiopurine dosing (26878724, 32598049, 28903549, 32308129, 29720126, 36858569, 35156873, 32221476, 31507415, 27577869, 27416873, 26033531, 32873882, 39688234).	{"Latino": 0.9728806, "European": 0.9931303, "East Asian": 0.9137417, "Central/South Asian": 0.93002415}	t
3685843	185	RYR1	c.12355A>T	Variant of uncertain significance	Uncertain function	\N	n/a	3685842	{35849058}	\N	\N	PS4_Sup	{"Latino": null, "American": null, "European": 0.00002941, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": 0.00002413}	f
3685847	185	RYR1	c.12398A>G	Variant of uncertain significance	Uncertain function	\N	n/a	3685846	{35849058}	\N	\N	PS4_Sup, PP3_Mod	{"Latino": 0.00006549, "American": null, "European": 0.0001029, "East Asian": null, "Near Eastern": null, "Central/South Asian": 0.0002075, "Sub-Saharan African": 0.00002412}	f
6481211	36	NAT2	*21	\N	Uncertain function	\N	\N	6481210	{19909761}	Inadequate	\N	NAT2*21 is assigned uncertain function based on inadequate evidence. NAT2*21 is characterized by the core SNVs c.458C>T (p.T153I) and c.803G>A (p.R268K). c.803G>A defines NAT2*4, formerly considered the reference allele, which has repeatedly shown normal function in vivo and in vitro. Published in silico modeling of c.458C>T (p.T153I) predicts that this variant impairs protein function based on the exposure of hydrophobic residues that may facilitate protein aggregation and/or targeted protein degradation (19909761). However, nine out of ten variant effect predictors tested by CPIC staff predict that c.458C>T (p.T153I) is neutral for NAT2 protein function and structure-based tools predict that this variant may increase protein stability.	\N	f
778430	375	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
778869	346	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
3685743	185	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
777723	394	CYP2C9	*28	Decreased function	Decreased function	\N	0.5	777722	{23752738,19541829,16788382}	Limited	\N	CYP2C9*28 is assigned decreased function based on limited evidence. Multiple in vitro studies found CYP2C9*28 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
3685703	185	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
6481233	36	NAT2	*38	Slow	Decreased function	\N	\N	6481232	{19909761}	Moderate	\N	NAT2*38 is assigned decreased function based on moderate evidence. NAT2*38 is characterized by the core SNVs c.590G>A (p.R197Q), c.766A>G (p.K256E) 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.766A>G (p.K256E) does not alter protein function (19909761). Four out of ten variant effect predictors tested by CPIC staff predict that c.766A>G 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 ten variant effect predictors tested by CPIC staff predict that c.590G>A impairs protein function. Thus, NAT2*38 is assigned decreased function based on c.590G>A. While c.766A>G is not predicted to impair protein function, it remains unknown whether there are any combinatorial effects associated with c.590G>A and c.766A>G.	\N	f
778193	389	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
3685335	185	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
2091249	294	CYP2D6	*158	\N	Unknown function	\N	n/a	2091248	{}	No Evidence	\N	CYP2D6*158 is assigned unknown function due to no literature describing function of this allele. CYP2D6*158 is defined by the three SNPs defining the decreased function *41 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": 0.00208, "African American/Afro-Caribbean": null}	f
3685523	185	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
3318594	139	CYP4F2	*12	\N	\N	\N	\N	3318593	\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
3318598	139	CYP4F2	*14	\N	\N	\N	\N	3318597	\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
778440	375	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
778767	346	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
6609707	31	CFTR	F508C,S1251N	\N	ivacaftor responsive	\N	\N	6606011	{}	\N	\N	\N	\N	f
6355344	39	CFTR	R117L	\N	ivacaftor responsive	\N	\N	6355343	{}	\N	\N	\N	\N	f
6355346	39	CFTR	R117P	\N	ivacaftor responsive	\N	\N	6355345	{}	\N	\N	\N	\N	f
6355348	39	CFTR	R170H	\N	ivacaftor responsive	\N	\N	6355347	{}	\N	\N	\N	\N	f
6355352	39	CFTR	R347L	\N	ivacaftor responsive	\N	\N	6355351	{}	\N	\N	\N	\N	f
777557	394	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
3685417	185	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
3685759	185	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
778105	390	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
778336	379	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
3685363	185	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
3685453	185	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
6355296	39	CFTR	I1027T	\N	ivacaftor responsive	\N	\N	6355295	{}	\N	\N	\N	\N	f
6355298	39	CFTR	I1139V	\N	ivacaftor responsive	\N	\N	6355297	{}	\N	\N	\N	\N	f
6355304	39	CFTR	L320V	\N	ivacaftor responsive	\N	\N	6355303	{}	\N	\N	\N	\N	f
6355306	39	CFTR	L967S	\N	ivacaftor responsive	\N	\N	6355305	{}	\N	\N	\N	\N	f
779085	152	NUDT15	*11	\N	Uncertain function	\N	\N	779084	{32094176}	Inadequate	\N	NUDT15*11 is assigned uncertain function based on inadequate evidence. An in vitro study expressed NUDT15*11 in HEK293 cells and found that protein expression and thiopurine sensitivity were comparable to cells expressing NUDT15*1 (32094176). Nine out of nine variant effect predictors tested by CPIC staff predict that the NUDT15*11-defining SNV (c.139G>A (p.G47R)) impairs protein function.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null}	f
779153	373	RYR1	c.130C>T	Likely Pathogenic	Malignant Hyperthermia associated	\N	n/a	779152	{33767344}	\N	\N	PS3_Mod, 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
777455	394	CYP2B6	*18	No function	No function	\N	\N	777454	{16272958,16495778,18281305,20517174,21746968,23080225,23344581,25878720,25897175,26655325,30085944,30201214,32238417,34115651,35538637}	Strong	\N	CYP2B6*18 (c. 983T>C, p.I328T) – No function: CYP2B6*18 is assigned no function (note that the formerly assigned CYP2B6*16 allele is now a suballele of CYP2B6*18). Several clinical studies indicate that CYP2B6*18 is strongly associated with higher plasma efavirenz exposure in patients with HIV (18281305, 23080225, 26655325). Studies evaluating efavirenz content in hair samples among patients with HIV taking efavirenz for more than three months found that patients with the CYP2B6*18 allele had nearly double efavirenz exposure compared to the *1 reference (26655325, 34115651). Another study evaluating plasma efavirenz concentrations in patients with HIV found three-fold higher efavirenz concentrations in patients carrying CYP2B6*18 compared to the *1 reference (16495778). Furthermore, CYP2B6*18 is associated with significantly higher exposure of nevirapine in plasma (18281305, 25878720) and hair (34115651) and lower exposure of hydroxybupropion after bupropion administration (23344581). Lower clearance of methadone compared to the *1 reference was found in a CYP2B6*18 carrier (35538637). Several in vitro studies found that CYP2B6*18 exhibited undetectable (or markedly decreased) protein expression and/or activity towards different probe substrates including efavirenz, bupropion, ketamine, and methadone, in several cDNA expression systems (16272958, 16495778, 20517174, 21746968, 25897175, 30085944, 30201214, 32238417, 35538637). Therefore, consensus among experts was no function based on strong evidence.	{"Latino": 0.014610389, "European": 0.0, "Oceanian": null, "East Asian": 0.0, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": 0.05768421, "African American/Afro-Caribbean": 0.03296694}	f
3827901	167	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
779077	374	NUDT15	*7	\N	No function	\N	\N	779076	{28659275,32094176,32221476,32873882}	Moderate	\N	NUDT15*7 is assigned no function based on moderate evidence. Patients carrying a NUDT15*7 allele tolerate lower doses of thiopurines (28659275 , 32873882 , 32221476 ). An in vitro study using a bacterial expression system found that NUDT15.7 enzymatic activity was undetectable and NUDT15.7 exhibited decreased protein thermostability compared to NUDT15.1 (28659275). An additional in vitro study expressed NUDT15*7 in HEK293 cells and found that the protein was expressed at similar levels to NUDT15.1, but cells were significantly more sensitive to thiopurine treatment (32094176). Nine out of nine variant effect predictors tested by CPIC staff predict that the NUDT15*7-defining SNV, c.101G>C (p.R34T), impairs protein function.	{"Latino": 0.0, "European": 0.0, "East Asian": 0.0005654, "Central/South Asian": 0.0}	f
3685599	185	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
3685617	185	RYR1	c.7075C>T	Variant of uncertain significance	Uncertain function	\N	n/a	3685616	{35849058}	\N	\N	PM1_Sup, PM5_Sup, PP3_Mod	{"Latino": 0.00006543, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": 0.00002414}	f
3685343	185	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
777467	394	CYP2B6	*24	\N	Uncertain function	\N	\N	777466	{20517174,21746968,30201214}	Inadequate	\N	CYP2B6*24 (c.1427G>A, p.G476D) – Uncertain function: CYP2B6*24 is assigned uncertain function. In vitro studies using cDNA expression systems found that CYP2B6*24 had no enzyme activity towards several substrates compared to the *1 reference (20517174, 21746968, 30201214). However, there was 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
778490	375	DPYD	c.3061G>C	Normal function	Normal function	\N	1.0	778489	{24648345}	Limited	\N	5-fluorouracil (in vitro)	{"Latino": 0.0, "European": 0.000090985195, "East Asian": 0.0, "Central/South Asian": 0.00010, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778915	346	G6PD	Loma Linda	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778914	{22293322,1999409}	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
779091	152	NUDT15	*14	\N	No function	\N	\N	779090	{}	Limited	\N	NUDT15*14 is assigned no function based on limited evidence. NUDT15*14 is characterized by the frameshift insertion c.80_81insCGGG (p.C28fs), which is predicted to impair protein function by CADD and PhD-SNPg. The insertion occurs in exon 1, which is within the Nudix hydrolase domain, and NUDT15*14 is predicted to produce a protein targeted for nonsense-mediated decay.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null}	f
779161	373	RYR1	c.742G>A	Likely Pathogenic	Malignant Hyperthermia associated	\N	n/a	779160	{33767344}	\N	\N	PS3_Mod, PS4, PM1, PP1, 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
3685717	185	RYR1	c.8189A>G	Variant of uncertain significance	Uncertain function	\N	n/a	3685716	{35849058}	\N	\N	PS4_Sup, PP1_St	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685753	185	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
3685755	185	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
3685795	185	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
779336	372	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
779165	373	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
3685421	185	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
3685425	185	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
779181	373	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
3685549	185	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	185	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
777449	394	CYP2B6	*14	Decreased function	Uncertain function	\N	\N	777448	{15190123,17559344,20517174,21746968,30201214}	Limited	\N	CYP2B6*14 (c.419G>A, p.R140Q) - Uncertain function: CYP2B6*14 is assigned uncertain function. In vitro studies using human liver microsomes (17559344, 15190123) and cDNA expression systems (15190123, 20517174, 30201214, 21746968) found that CYP2B6*14 has decreased enzyme activity compared to the *1 reference. However, due to the lack of any in vivo or clinical evidence, consensus among experts was uncertain clinical function based on limited evidence.	{"Latino": 0.0016818077, "European": 0.0050876285, "Oceanian": null, "East Asian": 0.0, "Near Eastern": null, "Central/South Asian": 0.002744161, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.0}	f
778352	381	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
778484	375	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
779033	346	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
778965	346	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
779441	372	TPMT	*23	\N	No function	\N	\N	779440	{17885628,18708949,23025308,31005613}	Limited	\N	TPMT*23 is assigned no function based on limited evidence. Erythrocytes from individuals genotyped TPMT*3A/*23 or *3C/*23 exhibited low activity (17885628). An in vitro study using a mammalian cell expression system found that TPMT.23 exhibited decreased affinity for 6-TG and TPMT.23 enzymatic activity is decreased by 40% compared to TPMT.1 (18708949). Published in silico modeling suggests that TPMT.23 exhibited decreased protein stability as well as altered substrate and co-factor binding (17885628, 23025308). Similarly, seven out of ten variant effect predictors tested by CPIC staff predict that the TPMT*23-defining SNV, c.500C>G (p.A167G), impairs protein function.	{"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
777741	394	CYP2C9	*37	Decreased function	Decreased function	\N	0.5	777740	{24077631,24118918,25142737,25144335,25951663,25476996,25832633,25884291,25924705,27163851,23844998}	Limited	\N	CYP2C9*37 is assigned decreased function based on limited evidence. Multiple in vitro studies found CYP2C9*37 demonstrated decreased clearance compared to wildtype with multiple substrates (24077631, 24118918, 25951663, 25476996, 25832633, 25924705, 27163851, 23844998). Although two in vitro studies showed CYP2C9*37 had similar 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 activity compared to wildtype in these studies (25142737, 25884291). An additional in vitro study showed CYP2C9*37 had similar activity compared to wildtype (25144335), however, the experts did not find this result convincing as the function of CYP2C9*37 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
4058605	101	CYP4F2	*17	\N	\N	\N	\N	4058604	\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
3685621	185	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
3685627	185	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
3685659	185	RYR1	c.7317G>C	Variant of uncertain significance	Uncertain function	\N	n/a	3685658	{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
779227	373	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
3685459	185	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
3685525	185	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
3685773	185	RYR1	c.10097G>A	Likely Benign	Normal function	\N	n/a	3685772	{33767344}	\N	\N	BS1	{"Latino": 0.002553, "American": null, "European": 0.001661, "East Asian": null, "Near Eastern": 0.001441, "Central/South Asian": 0.0008282, "Sub-Saharan African": 0.0001448}	f
777531	394	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
778207	296	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
778209	296	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
778410	377	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	377	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	377	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
778979	346	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
779292	372	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
3685383	185	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
3685543	185	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
3685733	185	RYR1	c.8638G>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685732	{35849058}	\N	\N	PS4_Sup, PP3_Mod	{"Latino": null, "American": null, "European": 0.0000147, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
777981	390	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
778011	390	CYP2D6	*39	\N	Normal function	\N	1.0	778010	{18784265,11266079,24647041,30366777}	Limited	\N	CYP2D6*39 is assigned normal function based on limited evidence. A liver microsomes sample of a subject with CYP2D6 *10/*39 genotype demonstrated similar enzyme activity compared to wildtype with a bufuralol substrate (11266079). Similarly, in vitro studies found CYP2D6*39 demonstrated similar enzyme activity compared to wildtype with bufuralol, dextromethorphan, and tamoxifen substrates (18784265, 24647041). Although one in vitro study found CYP2D6*39 demonstrated decreased clearance compared to wildtype with a primaquine substrate (30366777) the experts did not find this result convincing as CYP2D6*39 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": 0.008, "American": 0.001, "European": 0.014010031, "Oceanian": 0.0063141957, "East Asian": 0.0056442493, "Near Eastern": 0.026844444, "Central/South Asian": 0.0033921853, "Sub-Saharan African": 0.00080620806, "African American/Afro-Caribbean": 0.020066908}	f
778390	377	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
778713	346	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
778693	346	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
778785	346	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
778707	346	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
3685985	185	RYR1	c.14364+1G>T	Variant of uncertain significance	Uncertain function	\N	n/a	3685984	{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
777965	390	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
778819	346	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
778917	346	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
3685519	185	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
777491	394	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
777719	394	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
778029	390	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
779019	346	G6PD	Flores	II/Deficient	II/Deficient	\N	\N	779018	{22293322,15065213}	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
3685737	185	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
779229	373	RYR1	c.9310G>A	Likely Pathogenic	Malignant Hyperthermia associated	\N	n/a	779228	{33767344}	\N	\N	PS3_Mod, PS4_Mod, 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
3685811	185	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
3685815	185	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
3685823	185	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
3685825	185	RYR1	c.11958C>G	Variant of uncertain significance	Uncertain function	\N	n/a	3685824	{33767344}	\N	\N	PS4, PP1, BS3_Sup	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685961	185	RYR1	c.14782A>G	Variant of uncertain significance	Uncertain function	\N	n/a	3685960	{35849058}	\N	\N	PM1_Sup	{"Latino": null, "American": null, "European": 0.0000147, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
778849	346	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
2091251	294	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
778418	377	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
777773	394	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
778183	389	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
778392	377	DPYD	c.1294G>A	Normal function	Normal function	\N	1.0	778391	{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
3685837	185	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
3685871	185	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
778839	346	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
3685881	185	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
779233	373	RYR1	c.14387A>G	Variant of uncertain significance	Uncertain function	\N	n/a	779232	{}	\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
779241	373	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
3685911	185	RYR1	c.14270G>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685910	{35849058}	\N	\N	PM1_Sup, BP4	{"Latino": null, "American": null, "European": 0.0002352, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": 0.00007241}	f
779447	372	TPMT	*26	\N	No function	\N	\N	779446	{19660010}	Limited	\N	TPMT*26 is assigned no function based on limited evidence. An individual genotyped TPMT*1/*26 experienced hematological toxicity after standard azathioprine dosing and erythrocytes from the patient and two siblings also harboring TPMT*26 exhibited intermediate enzymatic activity (19660010). Four out of ten variant effect predictors tested by CPIC staff predict that the TPMT*26-defining SNV, c.622T>C (p.F208L), impairs protein function.	{"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
778488	375	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
778775	346	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
779189	373	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
778991	346	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
3685833	185	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
3685979	185	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
779288	373	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
777463	394	CYP2B6	*22	Normal or increased function	Uncertain function	\N	\N	777462	{15722458,17235330,17559344,20624854,35194103}	Inadequate	\N	CYP2B6*22 (c.-82T>C) – Uncertain function: CYP2B6*22 is assigned uncertain function. One study in human liver microsomes found that CYP2B6*22 had increased enzyme activity towards efavirenz and bupropion compared to the *1 reference (17559344). A second study found increased levels of CYP2B6*22 mRNA expression levels in human liver tissue and enzyme activity in liver microsomes compared to the *1 reference (15722458). A recent study using human liver tissues did not find increased mRNA content or activity (35194103); this study was limited by having only two samples genotyped as CYP2B6*1*22. Therefore, the consensus among experts was uncertain function based on inadequate evidence.	{"Latino": null, "European": 0.014, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": 0.031, "African American/Afro-Caribbean": 0.011}	f
777705	394	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
778143	389	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
778909	346	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
779191	373	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
778717	346	G6PD	Namouru	II/Deficient	II/Deficient	\N	\N	778716	{22293322,7825590}	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": 0.00020970956, "African American/Afro-Caribbean": 0.0}	f
110054	147	HLA-A	*31:01	\N	\N	\N	\N	9000	\N	\N	\N	\N	{"Latino": 0.04523886, "American": 0.061688375, "European": 0.026442025, "Oceanian": 0.010846613, "East Asian": 0.03451316, "Near Eastern": 0.011130483, "Central/South Asian": 0.03301915, "Sub-Saharan African": 0.007987001, "African American/Afro-Caribbean": 0.009934212}	f
779195	373	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
779197	373	RYR1	c.7007G>A	Pathogenic	Malignant Hyperthermia associated	\N	n/a	779196	{33767344}	\N	\N	PS3_Mod, PS4, PM1, PP1_St, PP3_Mod	{"Latino": null, "American": null, "European": 0.00009409, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
778875	346	G6PD	Seoul	II/Deficient	II/Deficient	\N	\N	778874	{22293322,28028996,1945893}	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
779087	152	NUDT15	*12	\N	Uncertain function	\N	\N	779086	{29519865,32094176}	Inadequate	\N	NUDT15*12 is assigned uncertain function based on inadequate evidence. An in vitro study expressed NUDT15*12 in HEK293 cells and found there was no effect on thiopurine sensitivity (32094176). An additional in vitro study found that NUDT15.12 exhibits decreased protein thermostability compared to NUDT15.1 (29519865). Patients carrying the NUDT15*12 allele had a 20% reduction in thiopurine dosing after the occurrence of adverse reactions (29519865). Seven out of nine variant effect predictors tested by CPIC staff predict that the NUDT15*12-defining SNV (c.156C>G (p.F52L)) impairs protein function.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null}	f
3685441	185	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
3685497	185	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
777747	394	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
778197	389	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
778378	377	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
778911	346	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
778723	346	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
779187	373	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
3827875	167	MT-RNR1	m.669T>C	\N	uncertain risk of aminoglycoside-induced hearing loss	\N	\N	3827874	{17637808,20353758}	Inadequate evidence	\N	MT-RNR1 669T>C is assigned an uncertain risk of aminoglycoside-induced hearing loss based on inadequate evidence. There are weak evidence proposing an association with aminoglycoside-induced hearing loss and this variant (17637808, 20353758). Therefore, consensus among experts was uncertain function due to insufficient evidence.	{"European": 0.0025295527, "East Asian": 0.0, "Near Eastern": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": null}	f
3685723	185	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
779298	372	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
779725	322	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
778897	346	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
778711	346	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
777771	394	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
1406320	376	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
778813	346	G6PD	Sibari	III/Deficient	III/Deficient	\N	\N	778812	{22293322,8447319}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": 0.0, "European": 0.000010243173, "East Asian": 0.0, "Central/South Asian": 0.0, "African American/Afro-Caribbean": 0.000036485697}	f
3685399	185	RYR1	c.1144C>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685398	{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
3685415	185	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
779203	373	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
3685785	185	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
779348	372	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
779183	373	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
3685579	185	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
779433	372	TPMT	*19	\N	Uncertain function	\N	\N	779432	{15652243,18708949}	Inadequate	\N	TPMT*19 is assigned uncertain function based on inadequate evidence. Erythrocytes from an individual genotyped TPMT*1/*19 exhibited normal activity (15652243). In an in vitro study using a yeast expression system, TPMT.19 activity was decreased by 30% relative to TPMT.1 using 6-TG as a substrate (15652243). Another in vitro study using a mammalian expression system found TPMT.19 enzymatic activity was decreased by 40% compared to TPMT.1 (18708949). Six out of ten variant effect predictors tested by CPIC staff predict that the TPMT*19-defining SNV, c.365A>C (p.K122T), impairs protein function.	{"Latino": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
777971	389	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
778386	377	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
777485	394	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
777571	394	CYP2C19	*22	\N	No function	\N	\N	777570	{25001882,19164093}	Limited	\N	CYP2C19*22 is assigned no function based on limited in vitro and computational evidence. An in vitro study found CYP2C19*22 had 8% enzyme activity compared to wildtype with a clopidogrel substrate and nondetectable enzyme activity compared to wildtype with a mephenytoin substrate (25001882). Crystal structure analysis shows the Arg186Pro substitution in CYP2C19*22 disrupts hydrogen bonds and alters protein structure resulting in decreased heme affinity and ultimately enzyme activity (19164093). 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": 0.0, "Oceanian": null, "East Asian": 0.0, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": 0.0}	f
778408	377	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
778482	375	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
778907	346	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
3685577	185	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
3685657	185	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
778673	346	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
779429	372	TPMT	*17	\N	No function	\N	\N	779428	{18708949,15226673}	Limited	\N	TPMT*17 is assigned no function based on limited evidence. Erythrocytes from an individual genotyped TPMT*1/*17 exhibited intermediate activity (15226673). An in vitro study using a mammalian cell expression system found that TPMT.17 exhibited decreased affinity for 6-TG and enzymatic activity is decreased by 90% compared to TPMT.1 (18708949). Three out of ten variant effect predictors tested by CPIC staff predict that the TPMT*17-defining SNV, c.124C>G (p.Q42E), impairs protein function.	{"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
778801	347	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
3685381	185	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
3685573	185	RYR1	c.6671G>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685572	{33767344}	\N	\N	PM1	{"Latino": 0.00006547, "American": null, "European": 0.0000735, "East Asian": null, "Near Eastern": null, "Central/South Asian": 0.000207, "Sub-Saharan African": null}	f
778356	381	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
777475	394	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
777599	394	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	376	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
778951	346	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
778949	346	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
3685559	185	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
779081	374	NUDT15	*9	\N	No function	\N	\N	779080	{28659275,30728528,39084859,30806694}	Strong	\N	NUDT15*9 is assigned no function based on strong evidence. An in vitro study using a bacterial expression system found that NUDT15.9 enzymatic activity was undetectable and NUDT15.9 exhibited decreased protein thermostability compared to NUDT15.1 (28659275). NUDT15*1/*9 patients exhibit decreased tolerance to thiopurines (28659275) and experience severe hematotoxicity (30728528, 30806694). NUDT15*9 is characterized by the deletion c.50delGAGTCG (p.del17_18GV), which is predicted to impair protein function by CADD and PhD-SNPg	{"Latino": 0.000259413, "European": 0.0018290388, "East Asian": 0.0, "Central/South Asian": 0.000494936}	f
3685741	185	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
3685831	185	RYR1	c.12064A>G	Variant of uncertain significance	Uncertain function	\N	n/a	3685830	{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
3685879	185	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
3685971	185	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
6481265	36	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). Five out of ten 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
3827881	167	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
3685351	185	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
3685587	185	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
1406316	376	CYP2C9	*72	Unknown function	Unknown function	\N	n/a	1406315	{}	No evidence	\N	CYP2C9*72 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
778181	389	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
778486	375	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
778969	346	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
778871	346	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
3827873	167	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
3685387	185	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
779169	373	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
3685477	185	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
3685503	185	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	185	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
3685775	185	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
3685969	185	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
3685349	185	RYR1	c.488G>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685348	{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": 0.00002413}	f
3685413	185	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
778133	389	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
3685419	185	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
2091259	294	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
778797	346	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
778987	346	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
778887	346	G6PD	Rehevot	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778886	{22293322,11112389}	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
3685899	185	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
779286	373	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
778151	389	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
778241	220	CYP4F2	*2	\N	\N	\N	\N	778240	\N	\N	\N	\N	{"Latino": 0.1669, "American": null, "European": 0.15959753, "East Asian": 0.084, "Near Eastern": 0.2107, "Central/South Asian": 0.1694, "Sub-Saharan African": 0.2329, "African American/Afro-Caribbean": null}	f
777549	394	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
778131	390	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
778338	381	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
778735	346	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
778747	346	G6PD	Ananindeua	II/Deficient	II/Deficient	\N	\N	778746	{22293322,32387609,12367584}	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
779029	346	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
779031	346	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
3827883	167	MT-RNR1	m.807A>G	\N	uncertain risk of aminoglycoside-induced hearing loss	\N	\N	3827882	{18830133}	Inadequate evidence	\N	MT-RNR1 807A>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 (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
3685331	185	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
3685801	185	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
3685339	185	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
3685855	185	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
3685369	185	RYR1	c.641C>T	Variant of uncertain significance	Uncertain function	\N	n/a	3685368	{35849058}	\N	\N	PS4_Mod, PM1, PP1, BS2_Mod, BS3_Sup	{"Latino": null, "American": null, "European": 0.0001911, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": 0.0001206}	f
3685439	185	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
3685583	185	RYR1	c.6757C>T	Variant of uncertain significance	Uncertain function	\N	n/a	3685582	{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
3685691	185	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
779173	373	RYR1	c.1565A>C	Pathogenic	Malignant Hyperthermia associated	\N	n/a	779172	{33767344}	\N	\N	PS3, 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
3685917	185	RYR1	c.14424C>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685916	{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
777489	394	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
777729	394	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
778394	377	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
778422	375	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
778677	346	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
1002692	366	SLCO1B1	*40	\N	Uncertain function	\N	\N	1002691	{11477075,21245207,32961594}	No evidence	\N	SLCO1B1*40 contains the rs4149056C>T variant that decreases function (also present in *5) and the rs34671512A>C variant that may increase function (present in *19 and *20). Based on evidence supporting the function of rs4149056C>T (11477075, 32961594, 21245207), SLCO1B1*40 is assigned uncertain function due to no 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
778861	346	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
778787	346	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
778827	346	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
777481	394	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
779011	346	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	346	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
777759	394	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
779694	322	CYP2D6	*3x2	\N	No function	\N	0.0	777940	{2211621}	Limited	\N	CYP2D6*3x2 is assigned no function based on limited evidence. CYP2D6*3 is defined by a single nucleotide deletion causing a frameshift and resulting in a nonfunctional protein and is assigned no function (2211621). 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": 0.00050, "American": null, "European": 0.00010, "Oceanian": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": 0.0}	f
3685581	185	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
778889	346	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
778867	346	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
778857	346	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
7219571	20	NAT2	*70	Slow	Decreased function	\N	\N	7219570	{15564878,35588539}	Limited	\N	NAT2*70 is assigned decreased function based on moderate evidence. An individual heterozygous for NAT2*70 experienced drug-induced hepatotoxicity after standard isoniazid dosing (35588539). NAT2*70 is defined by the core SNVs c.341T>C (p.I114T) and c.596T>C (p.I199T). c.341T>C (p.I114T) defines NAT2*5 which has been extensively studied, exhibiting decreased N-acetyltransferase activity both in vivo and in vitro. In vitro studies also show 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*70 would presumably be degraded in the same manner. Additionally, five out of ten variant effect predictors tested by CPIC staff predict that c.341T>C (p.I114T) impairs protein function. Three out of ten variant effect predictors tested by CPIC staff predict that c.596T>C (p.I199T) impairs protein function. NAT2*70 is assigned decreased function based on c.341T>C. Despite this, the combinatorial effects associated with c.341T>C and c.596T>C are uncertain.	\N	f
3685903	185	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
3685329	185	RYR1	c.190T>C	Variant of uncertain significance	Uncertain function	\N	n/a	3685328	{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
3685925	185	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
778169	389	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
779171	373	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
3685939	185	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
1002624	366	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
778171	389	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
778191	389	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
778239	220	CYP4F2	*1	\N	\N	\N	\N	778238	\N	\N	\N	\N	{"Latino": 0.5747943, "American": 0.5892313, "European": 0.56578875, "East Asian": 0.68352926, "Near Eastern": 0.43842018, "Central/South Asian": 0.42774868, "Sub-Saharan African": 0.6682824, "African American/Afro-Caribbean": 0.9237665}	t
778372	377	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
778995	346	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
778829	346	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
777573	394	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
777983	390	CYP2D6	*25	\N	Uncertain function	\N	n/a	777982	{24647041,30366777}	Inadequate	\N	CYP2D6*25 is assigned uncertain function due to inadequate evidence. In vitro studies found CYP2D6*25 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. Therefore, uncertain function was assigned.	{"Latino": null, "American": null, "European": 0.0, "Oceanian": 0.0, "East Asian": 0.0, "Near Eastern": 0.0, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": 0.0}	f
777989	390	CYP2D6	*28	\N	Uncertain function	\N	n/a	777988	{24647041,30366777}	Inadequate	\N	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.	{"Latino": null, "American": 0.0009319079, "European": 0.004213198, "Oceanian": null, "East Asian": 0.00021425438, "Near Eastern": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.0}	f
3318596	139	CYP4F2	*13	\N	\N	\N	\N	3318595	\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
778685	346	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
778925	346	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
778985	346	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
778759	346	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
778833	346	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
779093	152	NUDT15	*15	\N	Uncertain function	\N	\N	779092	{32094176}	Inadequate	\N	NUDT15*15 is assigned uncertain function based on inadequate evidence. An in vitro study expressed NUDT15*15 in HEK293 cells and found that NUDT15*15 protein levels were comparable to NUDT15*1 and NUDT15*15 had no effect on thiopurine sensitivity in cells (32094176). Five out of nine variant effect predictors tested by CPIC staff predict that c.467T>A (p.L156Q) impairs protein function.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null}	f
3685333	185	RYR1	c.251C>T	Variant of uncertain significance	Uncertain function	\N	n/a	3685332	{35849058}	\N	\N	PS3_Mod, PM1	{"Latino": null, "American": null, "European": 0.00001472, "East Asian": 0.0009731, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685605	185	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
3685907	185	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
6235914	41	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
778153	389	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
3685373	185	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
3685407	185	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
779491	373	UGT1A1	*6	\N	Decreased function	\N	\N	779490	{7715297,8280139,15179405,11906189}	\N	\N	15179405: SNS-38 (in vivo) - based on protein quantification; 11906189: bilirubin (in vivo) - based on protein quantification	{"Latino": 0.011556196, "European": 0.007872763, "Oceanian": null, "East Asian": 0.1463455, "Near Eastern": 0.0, "Central/South Asian": 0.044862628, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.003986928}	f
777731	394	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
3685465	185	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
777743	394	CYP2C9	*38	Decreased function	Decreased function	\N	0.5	777742	{24077631,24118918,25142737,25144335,25951663,25476996,25832633,25884291,25924705,27163851,28758225,23844998}	Limited	\N	CYP2C9*38 is assigned decreased function based on limited evidence. Multiple in vitro studies found CYP2C9*38 demonstrated decreased clearance compared to wildtype for multiple substrates (24077631, 24118918, 25144335, 25951663, 25476996, 25832633, 25884291, 25924705, 23844998). Although two in vitro studies showed CYP2C9*38 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 activity and similar activity compared to wildtype in these studies (25142737, 27163851). Additionally, the experts did not deem an in vitro study where CYP2C9*38 demonstrated activity ranging from decreased to increased compared to wildtype with 7-ethoxycoumarin, flavanone, and steroid substrates (28758225) as convincing evidence because it could not be ruled out that these results which differed from the majority of in vitro studies were due to the specific system used in the study. 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": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778374	377	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
779493	373	UGT1A1	*27	\N	Decreased function	\N	\N	779492	{7565971,7715297,15179405}	\N	\N	7715297: bilirubin (in vivo) - based on protein quantification; 15179405: SNS-38 (in vivo) - based on protein quantification	{"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
778416	375	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
3685783	185	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	185	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
779403	372	TPMT	*4	\N	No function	\N	\N	779402	{9246020,9486974,12880540}	Strong	\N	TPMT*4 is assigned no function based on strong evidence. The SNV characteristic of TPMT*4 (c.626-1G>A) is located in the splice junction between intron 9 and exon 10 and disrupts the canonical splice site, resulting in production of a truncated protein. Erythrocytes from individuals heterozygous for TPMT*4 exhibited intermediate TPMT enzymatic activity (9486974, 12880540), while erythrocytes from individuals carrying TPMT*4 in combination with another no function allele had very low TPMT enzymatic activity (9246020, 9486974). The in silico variant effect predictors, CADD and PhD-SNPg, predict that the TPMT*4-deifning SNV, c. 626-1G>A, impairs protein function. Additionally, c.626-1G>A is predicted to result in the loss of the acceptor splice site by SpliceAI.	{"Latino": 0.0, "European": 0.000058889815, "East Asian": 0.0, "Near Eastern": null, "Central/South Asian": 0.0, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778103	390	CYP2D6	*92	\N	No function	\N	0.0	778102	{25469868,26310775,26666748,26544071,26406933,27109434,27097346,27016952,26542054,26937172,26968424,27203132,27251229,27354764,27538917}	Limited	\N	CYP2D6*92 is assigned no function based on limited evidence. Multiple in vitro studies found CYP2D6*92 had nondetectable enzyme with various substrates (25469868, 26310775, 26666748, 26544071, 26406933, 27109434, 27097346, 27016952, 26542054, 26937172, 26968424, 27203132, 27251229, 27354764, 27538917). CYP2D6*92 is defined by a deletion resulting in a frameshift and early stop codon and 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
2091243	294	CYP2D6	*155	\N	Unknown function	\N	n/a	2091242	{}	No Evidence	\N	CYP2D6*155 is assigned unknown function due to no literature describing function of this allele. CYP2D6*155 is defined by the five SNPs defining the decreased function *29 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": 0.00104, "African American/Afro-Caribbean": null}	f
778771	346	G6PD	Ilesha	III/Deficient	III/Deficient	\N	\N	778770	{22293322,7959686,848857}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": 0.0011765126, "European": 0.000009013232, "East Asian": 0.0, "Central/South Asian": 0.00041928721, "African American/Afro-Caribbean": 0.00052700925}	f
3685367	185	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
779449	372	TPMT	*27	\N	No function	\N	\N	779448	{19945438}	Limited	\N	TPMT*27 is assigned no function based on limited evidence. Erythrocytes from an individual genotyped TPMT*1/*27 exhibited intermediate enzymatic activity and the patient received a reduced dose of azathioprine (19945438). An in vitro study using a mammalian cell expression system found that TPMT.27 exhibited decreased protein expression that is attributed to enhanced protein degradation by the proteasome, as well as clearance by autophagy (19945438). TPMT.27 expressed in mammalian cells exhibited 90% decreased enzymatic activity compared to TPMT.1 (19945438). Molecular dynamics simulations suggest that TPMT.27 exhibited decreased protein stability (19945438). In line with these results, nine out of ten variant effect predictors tested by CPIC staff predict that the TPMT*27-defining SNV, c.319T>G (p.Y107D), impairs protein function.	{"Latino": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
779497	372	UGT1A1	*36	\N	Increased function	\N	\N	779496	{9653159}	\N	\N	\N	{"Latino": 0.0, "European": 0.0, "Oceanian": 0.0, "East Asian": 0.0, "Near Eastern": 0.007933025, "Central/South Asian": 0.0, "Sub-Saharan African": 0.069839545, "African American/Afro-Caribbean": 0.084452555}	f
3685527	185	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
777577	394	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
777941	390	CYP2D6	*3	\N	No function	\N	0.0	777940	{2211621}	Limited	\N	CYP2D6*3 is assigned no function based on limited evidence. CYP2D6*3 was first described in a heterozygous subject demonstrating decreased sparteine metabolism based on an elevated urinary metabolite ratio. CYP2D6*3 is defined by a single nucleotide deletion causing a frameshift and resulting in a nonfunctional protein (2211621). 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": 0.0071793622, "American": 0.000654978, "European": 0.015922716, "Oceanian": 0.0010404624, "East Asian": 0.0000556167, "Near Eastern": 0.0043491097, "Central/South Asian": 0.0012986185, "Sub-Saharan African": 0.0009698735, "African American/Afro-Caribbean": 0.0032821998}	f
778065	390	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
778203	296	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
779503	372	UGT1A1	*80+*28	\N	Decreased function	\N	\N	779502	{21309756,19414484,22085899,19419973}	\N	UGT1A1*80 is in very high linkage disequilibrium with *28 and *37. However, the function of the *80 allele alone, in the absence of *28 or *37, is uncertain. If a patient is only tested for *80, decreased function may be inferred.	\N	{"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
777737	394	CYP2C9	*35	No function	No function	\N	0.0	777736	{23752738,24322786,2145143}	Limited	\N	CYP2C9*35 is assigned no function based on limited evidence in one heterozygous subject and in vitro studies. CYP2C9*35 was first described in a patient requiring a very low weekly warfarin dose of 2.25mg (2145143). No variant was observed in VKORC1 or CYP4F2 in this patient and a subsequent in silico study showed a decreased interaction with reductase resulting in impaired enzyme activity. In vitro studies similarly found CYP2C9*35 demonstrated no enzyme activity with warfarin, tolbutamide, and diclofenac substrates (23752738, 24322786). 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": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778093	390	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
778145	389	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
1777312	296	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
778695	346	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
778729	346	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
3685697	185	RYR1	c.7777C>G	Variant of uncertain significance	Uncertain function	\N	n/a	3685696	{35849058}	\N	\N	None	{"Latino": 0.00006607, "American": null, "European": 0.00001475, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685719	185	RYR1	c.8198G>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685718	{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
779245	373	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
1002700	366	SLCO1B1	*44	\N	Unknown function	\N	\N	1002699	{}	No evidence	\N	SLCO1B1*44 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.	{"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
3685371	185	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
3685557	185	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
3685567	185	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
3685625	185	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
778013	390	CYP2D6	*40	\N	No function	\N	0.0	778012	{12152006,12811367,24647041,30366777}	Moderate	\N	CYP2D6*40 is assigned no function based on moderate evidence in heterozygous subjects and in vitro studies. CYP2D6*40 is defined by an 18 base pair insertion. CYP2D6*40 has been described in subjects with CYP2D6 *4/*40, CYP2D6 *6/*40, and CYP2D6 *40/*42 genotype demonstrating poor metabolism with a dextromethorphan substrate (12152006, 12811367). Multiple in vitro studies found CYP2D6*40 had nondetectable enzyme activity compared to wildtype with various substrates (24647041, 30366777). Therefore, consensus among experts was no function with an activity value of 0 based on moderate evidence.	{"Latino": null, "American": 0.0, "European": 0.00069944287, "Oceanian": 0.0, "East Asian": 0.0, "Near Eastern": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": 0.013845487, "African American/Afro-Caribbean": 0.004642406}	f
778045	390	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
778073	390	CYP2D6	*72	\N	Uncertain function	\N	n/a	778072	{19158312,24647041,30366777}	Inadequate	\N	CYP2D6*72 is assigned uncertain function due to inadequate evidence. In vitro studies found CYP2D6*72 demonstrated decreased enzyme activity compared to wildtype with various substrates (19158312, 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": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778095	390	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
3685715	185	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
3685853	185	RYR1	c.12532G>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685852	{33767344}	\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
778382	377	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
778396	377	DPYD	c.1349C>T	Normal function	Normal function	\N	1.0	778395	{24648345}	Limited	\N	5-fluorouracil (in vitro)	{"Latino": 0.00008888889, "European": 0.0, "East Asian": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": 0.003892857, "African American/Afro-Caribbean": 0.0}	f
778823	346	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
3685535	185	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
3685613	185	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
2784577	168	CYP4F2	*6	\N	\N	\N	\N	2784576	\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
2784579	168	CYP4F2	*7	\N	\N	\N	\N	2784578	\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
3318586	139	CYP4F2	*8	\N	\N	\N	\N	3318585	\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
3318588	139	CYP4F2	*9	\N	\N	\N	\N	3318587	\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
7721585	6	CYP2C19	*42	\N	\N	\N	\N	7721584	\N	\N	\N	\N	\N	f
777543	394	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
6235910	41	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
778855	346	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
778675	346	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
3827911	167	MT-RNR1	m.1494C>T	Conformational change to the mitochondrial 12s rRNA leading to binding of aminoglycoside antibiotics	increased risk of aminoglycoside-induced hearing loss	\N	\N	3827910	{14681830,16380089,17085680,17434445,17698030,17698299,18830133,19682603,20100600,21205314,27397648,29876232,15722487,14681831,19687236,28103015,25474306}	Strong	\N	MT-RNR1 1494C>T is assigned an increased risk of aminoglycoside-induced hearing loss based on strong evidence. Screening of individuals or probands of individuals with aminoglycoside-hearing looss identified 1494C>T in a number of cases (14681830, 16380089, 17085680, 17434445, 17698030, 17698299, 18830133, 19682603, 20100600, 21205314, 27397648, 29876232). LCLs and/or cybrind cell lines with 1494C>T mutation have reduced growth in the presence of aminoglycosides (14681830, 15722487). Paromomycin shows increased binding to rRNA constructs carrying the T allele (19687236). Increased Kd for neomycin binding to A-site constructs carrying the T allele compared to those carrying the C allele (28103015). Cybrid lines with the 1494C>T mutation grown in gentamicin have reduced ATP production and altered mitochondria morphology (25474306). Therefore, consensus among experts was this variant is associated with increased risk of aminoglycoside-induced hearing loss based on strong evidence.	{"European": 0.00034900234, "East Asian": 0.0, "Near Eastern": 0.0, "Central/South Asian": 0.0006698, "Sub-Saharan African": 0.0}	f
3685699	185	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
3685729	185	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
777473	394	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
6481255	36	NAT2	*49	Slow	Decreased function	\N	\N	6481254	{19909761}	Moderate	\N	NAT2*49 is assigned decreased function based on moderate evidence. NAT2*49 is characterized by the core SNVs c.341T>C (p.I114T) and c.578C>T (p.T193M). Published in silico modeling predicts that c.578C>T (p.T193M) impairs protein function based on exposure of hydrophobic residues that may facilitate protein aggregation or targeted degradation (19909761). Similarly, six out of ten variant effect predictors tested by CPIC staff predict that c.578C>T (p.T193M) impairs protein function. c.341T>C (p.I114T) defines NAT2*5 which has repeatedly shown decreased N-acetyltransferase 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*49 would presumably be degraded in the same manner. Five out of ten variant effect predictors tested by CPIC staff predict that c.341T>C (p.I114T) impairs protein function. Thus, NAT2*49 is assigned decreased function based on c.341T>C. Despite this, it remains unknown whether there are any combinatorial effects associated with c.341T>C and c.578C>T	\N	f
778015	390	CYP2D6	*41	\N	Decreased function	\N	0.25	778014	{11037799,15289790,17001295,17112815,19364831}	Strong	\N	CYP2D6*41 is assigned decreased function based on strong evidence in heterozygous and homozygous subjects and in vitro studies. Subjects carrying CYP2D6*41 have demonstrated decreased enzyme activity compared to wildtype and CYP2D6*2 subjects with various substrates (11037799, 15289790, 17112815, 19364831). In vitro studies found CYP2D6*41 has decreased protein expression compared to wildtype (17001295, 19364831). Therefore, consensus among experts was decreased function with an activity value of 0.25 based on strong evidence.	{"Latino": 0.051015634, "American": 0.027095573, "European": 0.09237511, "Oceanian": 0.032435685, "East Asian": 0.023172446, "Near Eastern": 0.15358411, "Central/South Asian": 0.11927969, "Sub-Saharan African": 0.044932652, "African American/Afro-Caribbean": 0.037086975}	f
778681	346	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
778937	346	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
779017	346	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
778725	346	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
779179	373	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
778843	346	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
3685919	185	RYR1	c.14449A>T	Variant of uncertain significance	Uncertain function	\N	n/a	3685918	{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
779475	372	TPMT	*40	\N	Uncertain function	\N	\N	779474	{27564568,29785012}	Inadequate	\N	TPMT*40 is assigned uncertain function based on inadequate evidence. Erythrocytes from an individual genotyped TPMT*1/*40 exhibited intermediate enzymatic activity, however there was no difference in thiopurine dose intensity between TPMT*1/*1 patients and one patient genotyped TPMT*1/*40 (27564568). TPMT.40 exhibited comparable protein expression to TPMT.1 in mammalian cells (29785012). Three out of ten variant effect predictors tested by CPIC staff predict that the TPMT*40-defining SNV, c.677G>A (p.R226Q), impairs protein function.	{"Latino": 0.0002034, "European": 0.00005903421, "East Asian": 0.0, "Near Eastern": null, "Central/South Asian": 0.0, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
777559	394	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
778063	390	CYP2D6	*65	\N	Uncertain function	\N	n/a	778062	{24647041,30366777}	Inadequate	\N	CYP2D6*65 is assigned uncertain function due to inadequate evidence. In vitro studies found CYP2D6*65 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": 0.029529046, "Near Eastern": 0.0, "Central/South Asian": null, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": null}	f
778081	390	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
778360	381	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
778999	346	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
778931	346	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
778943	346	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
778023	390	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
3685357	185	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
778376	377	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
778913	346	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
3827907	167	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
3685397	185	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
779185	373	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
779025	346	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
779175	373	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
6355312	39	CFTR	L1480P	\N	ivacaftor responsive	\N	\N	6355311	{}	\N	\N	\N	\N	f
6355308	39	CFTR	L997F(G>C)	\N	ivacaftor responsive	\N	\N	6355307	{}	\N	\N	\N	\N	f
3685455	185	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
3685475	185	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
777597	394	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
1406322	376	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
3942828	164	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
3685473	185	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
778953	346	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
778891	346	G6PD	Insuli	IV/Normal	IV/Normal	\N	\N	778890	{22293322,12737940}	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
778863	346	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
3564277	197	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
3685575	185	RYR1	c.6670C>T	Likely Benign	Normal function	\N	n/a	3685574	{35849058}	\N	\N	PM1, BS1	{"Latino": null, "American": null, "European": 0.0001029, "East Asian": null, "Near Eastern": null, "Central/South Asian": 0.0006211, "Sub-Saharan African": 0.00004826}	f
3685677	185	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
6355310	39	CFTR	L997F(G>T)	\N	ivacaftor responsive	\N	\N	6355309	{}	\N	\N	\N	\N	f
3685747	185	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
6355314	39	CFTR	M152V	\N	ivacaftor responsive	\N	\N	6355313	{}	\N	\N	\N	\N	f
6355316	39	CFTR	M952I(G>A)	\N	ivacaftor responsive	\N	\N	6355315	{}	\N	\N	\N	\N	f
6355318	39	CFTR	M952I(G>C)	\N	ivacaftor responsive	\N	\N	6355317	{}	\N	\N	\N	\N	f
6355320	39	CFTR	M952I(G>T)	\N	ivacaftor responsive	\N	\N	6355319	{}	\N	\N	\N	\N	f
3685791	185	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
3685817	185	RYR1	c.11798A>G	Likely Benign	Normal function	\N	n/a	3685816	{33767344}	\N	\N	PP3_Mod, BS1	{"Latino": 0.002551, "American": null, "European": 0.001647, "East Asian": null, "Near Eastern": 0.001441, "Central/South Asian": 0.0008288, "Sub-Saharan African": 0.0000966}	f
6355322	39	CFTR	M952T	\N	ivacaftor responsive	\N	\N	6355321	{}	\N	\N	\N	\N	f
6355326	39	CFTR	Q237E	\N	ivacaftor responsive	\N	\N	6355325	{}	\N	\N	\N	\N	f
6355328	39	CFTR	Q237H	\N	ivacaftor responsive	\N	\N	6355327	{}	\N	\N	\N	\N	f
2677054	125	CYP2D6	*171	\N	\N	\N	\N	2677053	\N	\N	\N	\N	\N	f
7219581	20	NAT2	*75	Slow	Decreased function	\N	\N	7219580	{15564878}	Limited	\N	NAT2*75 is assigned decreased function based on moderate evidence. NAT2*75 is defined by the core SNVs c.264G>A (p.M88I) and c.341T>C (p.I114T). c.341T>C (p.I114T) defines NAT2*5 which has been extensively studied, exhibiting decreased N-acetyltransferase activity both in vivo and in vitro. In vitro studies also show 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*75 would presumably be degraded in the same manner. Additionally, five out of ten variant effect predictors tested by CPIC staff predict that c.341T>C (p.I114T) impairs protein function. There is no literature describing function for c.264G>A. Ten out of ten variant effect predictors tested by CPIC staff predict that c.264G>A (p.M88I) is neutral for protein function. NAT2*75 is assigned decreased function based on c.341T>C. Despite this, the combinatorial effects associated with c.341T>C and c.264G>A are uncertain.	\N	f
778879	346	G6PD	Ludhiana	II/Deficient	II/Deficient	\N	\N	778878	{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
3827915	167	MT-RNR1	m.1537C>T	\N	uncertain risk of aminoglycoside-induced hearing loss	\N	\N	3827914	{17637808}	Inadequate evidence	\N	MT-RNR1 1537C>T 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 (17637808). Therefore, consensus among experts was uncertain risk of aminoglycoside-induced hearing loss due to insufficient evidence.	{"European": 0.00038541437, "East Asian": 0.0, "Near Eastern": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": null}	f
3827919	167	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
3685355	185	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
779163	373	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
3685461	185	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
3685481	185	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	185	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
3685585	185	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
779201	373	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
777951	390	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
779167	373	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
3685489	185	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
3685597	185	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
1002694	366	SLCO1B1	*41	\N	No function	\N	\N	1002693	{39511784,34887219,27602404,39644095,40047317,22232210,35631530}	Strong	\N	SLCO1B1*41 is assigned no function based on strong evidence. SLCO1B1*41 is defined by c.481+1G>T which disrupts a canonical splice site. An individual genotyped SLCO1B1*31/*41 exhibited an elevated plasma concentration of coproporphyrin I, at a level comparable to that in SLCO1B1*15/*15 patients (39511784). Individuals compound heterozygous for *41 experienced statin-induced rhabdomyolysis (34887219, 39511784). SLCO1B1*41 was significantly associated with altered hexadecanedioate and SLCO1B1-associated oxylipins levels in individuals with *41 vs those without (27602404, 39644095). A large clinical study demonstrated that individuals with SLCO1B1*41 exhibited significantly increased bilirubin levels relative to those without, however there was no significant association with statin-induced myotoxicity (40047317). Additionally, SLCO1B1 loss-of-function has been implicated in the pathogenesis of Rotor syndrome and SLCO1B1*41 has been identified in affected families (22232210). The variant effect predictors CADD and PhD-SNPg predict that c.481+1G>T impairs protein function, which is supported by a published in silico analysis (35631530). Expression of a truncated protein due to aberrant splicing is also supported by SpliceAI predictions.	{"American": null, "European": 0.00010, "Oceanian": null, "East Asian": 0.0, "Near Eastern": null, "Central/South Asian": 0.0, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
6481261	36	NAT2	*52	Slow	Decreased function	\N	\N	6481260	{29273096}	Moderate	\N	NAT2*52 is assigned decreased function based on moderate evidence. NAT2*52 is characterized by the core SNVs c.518A>G (p.K173R), 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.518A>G (p.K173R). Ten out of ten variant effect predictors tested by CPIC staff predict that c.518A>G (p.K173R) is neutral for protein function. Similarly, published in silico analysis indicates that c.518A>G does not alter protein function (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 ten variant effect predictors tested by CPIC staff predict that c.590G>A (p.R197Q) impairs protein function. Thus, NAT2*52 is assigned decreased function based on c.590G>A. While c.518A>G is not predicted to impair protein function, the combinatorial effects associated with c.590G>A and c.518A>G are uncertain.	\N	f
2899163	183	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
777749	394	CYP2C9	*41	Uncertain function	Uncertain function	\N	n/a	777748	{24077631,24118918,25142737,25951663,25144335,25476996,25614704,25832633,25884291,25924705,27163851,23844998}	Inadequate evidence	\N	CYP2C9*41 is assigned uncertain function due to inadequate evidence in one heterozygous subject and in vitro studies. One subject with CYP2C9 *1/*41 genotype exhibited increased AUC but similar oral clearance compared to wildtype subjects based on tolbutamide plasma concentrations after one 500mg dose (25614704). In vitro studies found CYP2C9*41 demonstrated enzyme activity ranging from decreased to increased compared to wildtype with various substrates (24077631, 24118918, 25142737, 25144335, 25951663, 25476996, 25832633, 25884291, 25924705, 27163851, 23844998, 25614704). 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
778187	389	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
778803	346	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
3685337	185	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
778761	346	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
3685405	185	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
778795	346	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
3685721	185	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
3685769	185	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
3685807	185	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
778993	346	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
778733	346	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
778757	346	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
3685341	185	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
3685353	185	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
777314	240	CFTR	3849+10kbC->T	\N	ivacaftor responsive	\N	\N	777313	{}	\N	ACMG screening panel	\N	\N	f
777326	240	CFTR	D1152H	\N	ivacaftor responsive	\N	\N	777325	{}	\N	\N	\N	\N	f
3685739	185	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
778705	346	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
6235064	28	CYP2C19	*40	\N	\N	\N	\N	6235063	\N	\N	\N	\N	\N	f
777967	390	CYP2D6	*17	\N	Decreased function	\N	0.5	777966	{8764380,8971426,9415713,11823760,24647041,30366777}	Moderate	\N	CYP2D6*17 is assigned decreased function based on moderate evidence. CYP2D6*17 has consistently been described in heterozygous and homozygous subjects demonstrating decreased metabolism of various CYP2D6 substrates compared to wildtype subjects based on urine metabolites (8764380, 8971426, 11823760). Multiple in vitro studies found CYP2D6*17 had at least modestly decreased enzyme activity compared to wildtype with various substrates (9415713, 24647041, 30366777). Therefore, consensus among experts was decreased function with an activity value of 0.5 based on moderate evidence.	{"Latino": 0.023261126, "American": 0.0052698795, "European": 0.0039216722, "Oceanian": 0.0010413943, "East Asian": 0.00009343609, "Near Eastern": 0.030970177, "Central/South Asian": 0.0004806022, "Sub-Saharan African": 0.19355686, "African American/Afro-Caribbean": 0.16882424}	f
6235066	28	CYP2C19	*41	\N	\N	\N	\N	6235065	\N	\N	\N	\N	\N	f
3685821	185	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
2899151	183	CYP2B6	*43	Decreased function	Decreased function	\N	\N	2899150	{14551287,18171905,24260284,38596098}	Limited	\N	CYP2B6*43 (c.516G>T, p.Q172H/splice defect; c.785A>G, p.K262R; c.1390G>A, p.A464T) – Decreased function: CYP2B6*43 is assigned decreased function. CYP2B6*43 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.A464T 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
777561	394	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
778853	346	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
778719	346	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
778781	348	G6PD	Taipei, Chinese-3	II/Deficient	II/Deficient	\N	\N	778780	{22293322,1562739}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": 0.0, "European": 0.0, "East Asian": 0.0008090069, "Central/South Asian": 0.0, "African American/Afro-Caribbean": 0.0}	f
3685923	185	RYR1	c.14458G>T	Variant of uncertain significance	Uncertain function	\N	n/a	3685922	{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
777479	394	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
777585	394	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
3685967	185	RYR1	c.14814C>G	Variant of uncertain significance	Uncertain function	\N	n/a	3685966	{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
778444	375	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
777801	376	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
6235321	28	CYP2C9	*86	\N	\N	\N	\N	6235320	\N	\N	\N	\N	\N	f
6235323	28	CYP2C9	*87	\N	\N	\N	\N	6235322	\N	\N	\N	\N	\N	f
6235325	28	CYP2C9	*88	\N	\N	\N	\N	6235324	\N	\N	\N	\N	\N	f
2091257	294	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
778384	377	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
777364	240	CFTR	R117C	\N	ivacaftor responsive	\N	\N	777363	{}	\N	\N	\N	\N	f
777366	240	CFTR	R117H	\N	ivacaftor responsive	\N	\N	777365	{}	\N	ACMG screening panel	\N	\N	f
777368	240	CFTR	R347H	\N	ivacaftor responsive	\N	\N	777367	{}	\N	\N	\N	\N	f
777370	240	CFTR	R352Q	\N	ivacaftor responsive	\N	\N	777369	{}	\N	\N	\N	\N	f
777374	240	CFTR	S1251N	\N	ivacaftor responsive	\N	\N	777373	{}	\N	\N	\N	\N	f
2899161	183	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
778364	381	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
778380	377	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
778927	346	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
779221	373	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
3685709	185	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
3685849	185	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
3685321	185	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
777595	394	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
779712	322	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
778039	390	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
778448	375	DPYD	c.2186C>T	Normal function	Normal function	\N	1.0	778447	{24648345}	Limited	\N	5-fluorouracil (in vitro)	{"Latino": 0.0, "European": 0.00001364734, "East Asian": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
3685501	185	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
777493	394	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
777701	394	CYP2C9	*17	Uncertain function	Uncertain function	\N	n/a	777700	{23752738,16099926}	Inadequate evidence	\N	CYP2C9*17 is assigned uncertain function based on inadequate evidence due to conflicting in vitro data and no clinical data. In an in vitro study CYP2C9*17 demonstrated 32% warfarin clearance compared to wildtype, however, similar tolbutamide clearance compared to wildtype was demonstrated in the same study as well as a separate study (23752738, 16099926). Therefore, consensus among experts was not achieved and 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
778089	389	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
778189	389	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
1103378	296	CYP2D6	*146	\N	Uncertain function	\N	n/a	1103377	{}	Inadequate	\N	CYP2D6*146 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 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
777943	390	CYP2D6	*4	\N	No function	\N	0.0	777942	{2211621,11266079,1978251,1978565}	Strong	\N	CYP2D6*4 is assigned no function based on strong evidence. CYP2D6*4 has consistently been described in subjects demonstrating decreased metabolism of various CYP2D6 substrates (2211621, 11266079, 1978251, 1978565). Two in vitro studies found CYP2D6*4 had undetectable protein expression (2211621, 11266079). CYP2D6*4 is defined by a splicing defect resulting in a nonfunctional protein. Therefore, consensus among experts was no function with an activity value of 0 based on strong evidence.	{"Latino": 0.12051356, "American": 0.10194215, "European": 0.1848476, "Oceanian": 0.017797798, "East Asian": 0.005269325, "Near Eastern": 0.11405941, "Central/South Asian": 0.089567736, "Sub-Saharan African": 0.028676093, "African American/Afro-Caribbean": 0.048111428}	f
5294109	88	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
3685509	185	RYR1	c.5132A>G	Variant of uncertain significance	Uncertain function	\N	n/a	3685508	{35849058}	\N	\N	PS4_Sup, PP1_Sup, PS3_Mod	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": 0.00004827}	f
778350	381	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
778743	346	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
778709	346	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
777711	394	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
779734	323	CYP2D6	*36x2	\N	No function	\N	0.0	778004	{12439227}	Limited	\N	CYP2D6*36x2 is assigned no function based on limited evidence in a heterozygous subject. CYP2D6*36x2 has been described in a subject with CYP2D6*21/*36x2 genotype demonstrating poor metabolism with a debrisoquine substrate (12439227). 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": 0.00050, "American": 0.0, "European": 0.0, "Oceanian": null, "East Asian": 0.004052432, "Near Eastern": null, "Central/South Asian": 0.0, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.000092301394}	f
778366	381	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
779421	372	TPMT	*13	\N	No function	\N	\N	779420	{16220112,18708949,13679074}	Limited	\N	TPMT*13 is assigned no function based on limited evidence. TPMT*13 was identified in an individual who experienced severe leucopenia after standard azathioprine dosing. In vitro studies found that TPMT.13 protein expression is decreased, enzymatic activity is decreased by 40-80%, and TPMT.13 exhibited decreased affinity for 6-MP, 6-TG, and SAM relative to TPMT.1 in mammalian (16220112, 18708949) and yeast cells (13679074). Six out of ten variant effect predictors tested by CPIC staff predict that the TPMT*13-defining SNV, c.83A>T (p.E28V), impairs protein function.	{"Latino": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
779443	372	TPMT	*24	\N	Uncertain function	\N	\N	779442	{18602085,27564568,29785012,33118454,34412101}	Inadequate	\N	TPMT*24 is assigned uncertain function based on inadequate evidence. Erythrocytes from individuals genotyped TPMT*1/*24 exhibited intermediate activity (18602085, 27564568), while erythrocytes from individuals genotyped TPMT*3A/*24 or *3C/*24 exhibited low enzymatic activity (33118454). There is no difference in thiopurine dose intensity observed between individuals genotyped TPMT*1/*1 and TPMT*1/*24 (27564568, 34412101). An in vitro study using a yeast expression system found that TPMT.24 exhibited decreased affinity for 6-TG, but the rate of enzymatic activity is unaffected compared to TPMT.1 (18602085). TPMT.24 exhibited comparable protein expression to TPMT.1 in mammalian cells (29785012). One out of ten variant effect predictors tested by CPIC staff predicts that the TPMT*24-defining SNV, c.537G>T (p.Q179H), impairs protein function.	{"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
6237970	28	SLCO1B1	*50	\N	\N	\N	\N	6237969	\N	\N	\N	\N	\N	f
6237972	28	SLCO1B1	*51	\N	\N	\N	\N	6237971	\N	\N	\N	\N	\N	f
6237974	28	SLCO1B1	*52	\N	\N	\N	\N	6237973	\N	\N	\N	\N	\N	f
6237976	28	SLCO1B1	*53	\N	\N	\N	\N	6237975	\N	\N	\N	\N	\N	f
777587	394	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
777985	390	CYP2D6	*26	\N	Uncertain function	\N	n/a	777984	{18838503,24647041,30366777}	Inadequate	\N	CYP2D6*26 is assigned uncertain function due to inadequate evidence. In vitro studies found CYP2D6*26 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": 0.0, "Oceanian": 0.0, "East Asian": 0.0, "Near Eastern": 0.0, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": 0.0}	f
778398	377	DPYD	c.1358C>G	Normal function	Normal function	\N	1.0	778397	{23588312}	Limited	\N	5-fluorouracil (in vitro)	{"Latino": 0.0, "European": 0.0, "East Asian": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": 0.002017857, "African American/Afro-Caribbean": 0.0030573248}	f
778402	377	DPYD	c.1403C>A	Normal function	Normal function	\N	1.0	778401	{24648345}	Limited	\N	5-fluorouracil (in vitro)	{"Latino": 0.0, "European": 0.000039617094, "East Asian": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.0}	f
778426	375	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
778751	346	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
110056	147	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
3827903	167	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
779483	152	TPMT	*44	\N	No function	\N	\N	779482	{31005613,32865889}	Moderate	\N	TPMT*44 is assigned no function based on moderate evidence. Erythrocytes from individuals genotyped TPMT*1/*44 exhibited intermediate enzymatic activity (31005613, 32865889). Recombinant TPMT.44 expressed in E coli. exhibited decreased protein stability (31005613) and protein abundance was low when expressed in mammalian cells (29785012). Ten out of ten variant effect predictors tested by CPIC staff predict that the TPMT*44-defining SNV, c.497A>G (p.Y166C), impairs protein function.	{"Latino": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
6237978	28	SLCO1B1	*54	\N	\N	\N	\N	6237977	\N	\N	\N	\N	\N	f
777715	394	CYP2C9	*24	No function	No function	\N	0.0	777714	{23752738,17332144,16543980}	Limited	\N	CYP2C9*24 is assigned decreased function based on limited evidence in a heterozygous patient and in vitro studies. A patient on a stable dose of warfarin with CYP2C9 *2/*24 genotype had the lowest daily warfarin dose requirement and warfarin clearance based on plasma concentrations compared to patients with CYP2C9 *1/*2 genotype and matched for age, warfarin indication and co-administrated medications (16543980). An in vitro study similarly found CYP2C9*24 exhibited no enzyme activity with warfarin or tolbutamide substrates (23752738). No CYP2C9*24 protein was detected in a separate in vitro study suggesting the enzyme may be improperly folded (17332144). 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": 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
778741	346	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
1002702	366	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
779015	346	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
777495	394	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
777687	394	CYP2C9	*10	Uncertain function	Uncertain function	\N	n/a	777686	{23752738,28758225,15284535}	Inadequate evidence	\N	CYP2C9*10 is assigned uncertain function based on conflicting in vitro data and no clinical data. Although CYP2C9*10 demonstrated decreased warfarin clearance (23752738) it also demonstrated similar activity with a tolbutamide substrate (15284535) and activity ranging from decreased to normal with 7-ethoxycoumarin, flavanone, and steroid substrates (28758225) compared to wildtype. Therefore, consensus among experts was not achieved and 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": 0.0, "African American/Afro-Caribbean": 0.0}	f
3685323	185	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
3685395	185	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
3685409	185	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
3685479	185	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
3685595	185	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
777779	394	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
779157	373	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
778041	390	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
778432	375	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	375	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
778454	375	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
779037	346	G6PD	Arakawa	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	779036	{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
778865	346	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
778773	346	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
3827913	167	MT-RNR1	m.1520T>C	\N	uncertain risk of aminoglycoside-induced hearing loss	\N	\N	3827912	{7550368}	Inadequate evidence	\N	MT-RNR1 1520T>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 (7550368). Therefore, consensus among experts was uncertain risk of aminoglycoside-induced hearing loss due to insufficient evidence.	{"European": 0.00016057443, "East Asian": 0.008772, "Near Eastern": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": null}	f
3685467	185	RYR1	c.2996G>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685466	{33767344}	\N	\N	None	{"Latino": 0.00006547, "American": null, "European": 0.0001176, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
778097	390	CYP2D6	*89	\N	Uncertain function	\N	n/a	778096	{25469868,26310775,26666748,26544071,26406933,27109434,27097346,27016952,26542054,26937172,26968424,27203132,27251229,27354764,27538917}	Inadequate	\N	CYP2D6*89 is assigned uncertain function due to inadequate evidence. In vitro studies found CYP2D6*89 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
2091253	294	CYP2D6	*160	\N	Unknown function	\N	n/a	2091252	{}	No Evidence	\N	CYP2D6*160 is assigned unknown function due to no literature describing function of this allele. CYP2D6*160 is defined by the two SNPs defining the normal function *2 allele and two additional SNPs that are also found on *82 which is cassified as unknown 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
778845	346	G6PD	Bangkok	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778844	{22293322,21302115}	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	346	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
778779	346	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
778679	346	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
778721	346	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
3685511	185	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
779193	373	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
3685571	185	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
777693	394	CYP2C9	*13	Decreased function	No function	\N	0.0	777692	{23752738,16308280,15764711,25951663,19541829,16740353,20814155,19604036,21395648,21726410,21842338,22735459,23844998,24118918,24464553,25142737,25476996,25614704,25832633,25884291,27163851,25144335,27377818,27864660,15606435,24077631}	Definitive	\N	CYP2C9*13 is assigned no function based on definitive evidence in heterozygous patients. Subjects with CYP2C9*1/*13 genotype repeatedly demonstrated decreased clearance and increased AUC compared to wildtype subjects and similar clearance and AUC compared to CYP2C9*1/*3 subjects in multiple studies with different substrates (19604036, 21395648, 21726410, 21842338, 22735459, 27377818, 27864660, 15606435). Two studies correlated in vitro data with clinical data and also found increased AUC and decreased clearance compared to wildtype with lornoxicam and tolbutamide (15764711, 25614704). Additionally, a CYP2C9*3/*13 subject had a greater decrease in tolbutamide clearance compared to the CYP2C9*1/*13 subject (25614704). This was also demonstrated in another CYP2C9*3/*13 subject with decreased lornoxicam clearance and increased AUC compared to wildtype, CYP2C9 *1/*3, and CYP2C9*1/*2 subjects (15606435). Multiple in vitro studies demonstrate CYP2C9*13 exhibits decreased metabolism comparable to that observed for CYP2C9*3 for numerous substrates (23844998, 24118918, 24464553, 25142737, 25476996, 25832633, 25884291, 27163851, 24077631, 25951663, 19541829, 20814155, 23752738, 16308280, 25144335) and one model suggests the decreased metabolism across substrates is due to a side chain rotation which blocks the catalytic site (16740353). Therefore, consensus among experts was no function with an activity value of 0 based on definitive evidence.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": 0.0033167014, "Near Eastern": 0.0, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": 0.0}	f
777949	390	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
778111	390	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
2091255	294	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
778404	377	DPYD	c.1475C>T	No function	No function	\N	0.0	778403	{24648345}	Limited	\N	5-fluorouracil (in vitro)	{"Latino": 0.0, "European": 0.0, "East Asian": 0.0, "Central/South Asian": 0.00020, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778793	346	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
778947	346	G6PD	Wisconsin	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778946	{22293322,16934959,7655862}	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
779021	346	G6PD	Yunan	Uncertain function	Uncertain function	\N	\N	779020	{22293322,11780463}	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
778667	347	G6PD	B (reference)	IV/Normal	IV/Normal	\N	\N	778666	{22293322,2572288}	limited	\N	Function assigned based on the WHO recommendations included in PMID 22293322.	{"Latino": 0.9772377, "European": 0.99463695, "East Asian": 0.97378683, "Central/South Asian": 0.9557555, "African American/Afro-Caribbean": 0.55657554}	t
3685457	185	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
778027	390	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	390	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
778083	389	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
778173	389	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
3685531	185	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
3685663	185	RYR1	c.7355G>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685662	{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
3685779	185	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
3685875	185	RYR1	c.13673G>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685874	{33767344}	\N	\N	PP3_Mod	{"Latino": null, "American": null, "European": 0.00002941, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
778939	346	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
778841	346	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
778805	346	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
3685615	185	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
777945	390	CYP2D6	*5	\N	No function	\N	0.0	777944	{1673290,11266079,31544239}	Definitve	\N	CYP2D6*5 is assigned no function based on definitive evidence. CYP2D6*5 has been studied for more than 20 years and its association with impaired function is well-established (1673290, 31544239). CYP2D6*5 is defined by a deletion of the CYP2D6 gene. CYP2D6*5 was first identified in a homozygous subject demonstrating decreased sparteine metabolism (1673290). An additional study found liver samples of seven subjects heterozygous for CYP2D6*5 demonstrated decreased intrinsic clearance compared to wildtype with a bufuralol substrate (11266079). Therefore, consensus among experts was no function with an activity value of 0 based on definitive evidence.	{"Latino": 0.02915789, "American": 0.01643337, "European": 0.029482473, "Oceanian": 0.03483003, "East Asian": 0.0482394, "Near Eastern": 0.018235605, "Central/South Asian": 0.041759778, "Sub-Saharan African": 0.06219285, "African American/Afro-Caribbean": 0.054194603}	f
777957	390	CYP2D6	*11	\N	No function	\N	0.0	777956	{8563771,9241659}	Limited	\N	CYP2D6*11 is assigned no function based on limited evidence. CYP2D6*11 is defined by a splicing defect yielding a nonfunctional enzyme and was identified in a subject demonstrating markedly decreased sparteine metabolism (8563771, 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": 0.0, "American": 0.0, "European": 0.000148423, "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": 0.00028528165}	f
778139	389	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
6235912	41	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
6355218	39	CFTR	A349V	\N	ivacaftor responsive	\N	\N	6355217	{}	\N	\N	\N	\N	f
777939	390	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
779235	373	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
778971	346	G6PD	Japan, Shinagawa	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778970	{22293322,8193373,1611091}	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
778933	346	G6PD	Madrid	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778932	{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
778877	346	G6PD	Omiya	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778876	{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
778955	346	G6PD	Puerto Limon	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778954	{22293322,7160841}	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
110057	141	HLA-B	*58:01	\N	\N	\N	\N	9003	\N	\N	\N	\N	{"Latino": 0.013537052, "American": 0.011914154, "European": 0.0076844515, "Oceanian": 0.014144436, "East Asian": 0.06041846, "Near Eastern": 0.018732347, "Central/South Asian": 0.041933447, "Sub-Saharan African": 0.04351446, "African American/Afro-Caribbean": 0.038205802}	f
779103	152	NUDT15	*20	\N	Uncertain function	\N	\N	779102	{32094176}	Inadequate	\N	NUDT15*20 is assigned uncertain function based on inadequate evidence. An in vitro study expressed NUDT15*20 in HEK293 cells and found NUDT15 protein expression and thiopurine sensitivity were comparable to cells expressing NUDT15*1 (32094176). Eight out of nine variant effect predictors tested by CPIC staff predict that the NUDT15*20-defining SNV (c.386C>G (p.P129R)) impairs protein function.	{"Latino": null, "European": null, "East Asian": null, "Central/South Asian": null}	f
6355214	39	CFTR	A120T	\N	ivacaftor responsive	\N	\N	6355213	{}	\N	\N	\N	\N	f
6355216	39	CFTR	A234D	\N	ivacaftor responsive	\N	\N	6355215	{}	\N	\N	\N	\N	f
779326	372	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
778001	390	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
778031	390	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
778149	389	CYP2D6	*115	\N	Unknown function	\N	n/a	778148	{}	No Evidence	\N	CYP2D6*115 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
778901	346	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
6481259	36	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 ten 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	39	CFTR	D192G	\N	ivacaftor responsive	\N	\N	6355227	{}	\N	\N	\N	\N	f
6355232	39	CFTR	D924N	\N	ivacaftor responsive	\N	\N	6355231	{}	\N	\N	\N	\N	f
6355242	39	CFTR	E822K	\N	ivacaftor responsive	\N	\N	6355241	{}	\N	\N	\N	\N	f
6355246	39	CFTR	F311del	\N	ivacaftor responsive	\N	\N	6355245	{}	\N	\N	\N	\N	f
6355248	39	CFTR	F311L	\N	ivacaftor responsive	\N	\N	6355247	{}	\N	\N	\N	\N	f
6355250	39	CFTR	F508C	\N	ivacaftor responsive	\N	\N	6355249	{}	\N	\N	\N	\N	f
6355258	39	CFTR	G178E	\N	ivacaftor responsive	\N	\N	6355257	{}	\N	\N	\N	\N	f
6355262	39	CFTR	G194R(G>A)	\N	ivacaftor responsive	\N	\N	6355261	{}	\N	\N	\N	\N	f
6355264	39	CFTR	G194R(G>C)	\N	ivacaftor responsive	\N	\N	6355263	{}	\N	\N	\N	\N	f
6355266	39	CFTR	G314E	\N	ivacaftor responsive	\N	\N	6355265	{}	\N	\N	\N	\N	f
778135	389	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
777338	240	CFTR	F1052V	\N	ivacaftor responsive	\N	\N	777337	{}	\N	\N	\N	\N	f
777340	240	CFTR	F1074L	\N	ivacaftor responsive	\N	\N	777339	{}	\N	\N	\N	\N	f
777342	240	CFTR	G1069R	\N	ivacaftor responsive	\N	\N	777341	{}	\N	\N	\N	\N	f
777344	240	CFTR	G1244E	\N	ivacaftor responsive	\N	\N	777343	{}	\N	\N	\N	\N	f
777346	240	CFTR	G1349D	\N	ivacaftor responsive	\N	\N	777345	{}	\N	\N	\N	\N	f
777354	240	CFTR	K1060T	\N	ivacaftor responsive	\N	\N	777353	{}	\N	\N	\N	\N	f
777360	240	CFTR	R1070Q	\N	ivacaftor responsive	\N	\N	777359	{}	\N	\N	\N	\N	f
777362	240	CFTR	R1070W	\N	ivacaftor responsive	\N	\N	777361	{}	\N	\N	\N	\N	f
6355272	39	CFTR	G576A	\N	ivacaftor responsive	\N	\N	6355271	{}	\N	\N	\N	\N	f
6355274	39	CFTR	G970D	\N	ivacaftor responsive	\N	\N	6355273	{}	\N	\N	\N	\N	f
779330	372	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
7726083	12	TPMT	*45	\N	No function	\N	\N	7726082	{33273844,34412101,29785012}	Limited	\N	TPMT*45 is assigned no function based on limited evidence. A patient genotyped TPMT*1/*45 exhibited low TPMT enzymatic activity and a plasma 6-TGN concentration above the therapeutic range (33273844). Following reduction of the thiopurine dosage, the patient's 6-TGN plasma concentration decreased and was within the therapeutic range (33273844). However, another patient genotyped TPMT*1/*45 tolerated a 6-MP dose of 73.1 mg/m2 (34412101). TPMT*45 results in the generation of a premature stop codon at residue 226 and the production of a truncated protein. The premature stop occurs upstream of the known "no function" variant (c.719A>G, defining TPMT*3C), suggesting that loss of this region of the protein alters function. Two out of four variant effect predictors tested by CPIC staff predict that the TPMT*45-defining SNV, c.676C>T (p.R226X), impairs protein function. In a study of variant abundance by massively parallel sequencing, the TPMT*45 variant was found to have low protein abundance (29785012).	{"Latino": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
778959	346	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
6481277	36	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). Ten out of ten variant effect predictors tested by CPIC staff predict that c.491T>C (p.I164T) is neutral for protein function	\N	f
778727	346	G6PD	Guangzhou	III/Deficient	III/Deficient	\N	\N	778726	{22293322,16607506}	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
778885	346	G6PD	Manhattan	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778884	{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
778981	346	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
3685365	185	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
777469	393	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
777487	394	CYP2B6	*34	Decreased function	Decreased function	\N	\N	777486	{23418033,30201214,18171905,24260284}	Limited	\N	CYP2B6*34 (c.-82T>C, c.516G>T, p.Q172H/splice defect; c.785A>G, p.K262R; c.1459C>A, p.R487S) – Decreased function: CYP2B6*34 is assigned decreased function. CYP2B6*34 contains c.516G>T which causes aberrant splicing (see CYP2B6*6 for more information) (23418033). Although one in vitro study using a cDNA expression system found that CYP2B6*34 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*34. 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
2899157	183	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
778358	379	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
778919	346	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
778873	346	G6PD	West Virginia	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778872	{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
777539	394	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
779419	372	TPMT	*12	\N	Uncertain function	\N	\N	779418	{18708949,13679074,27564568,16220112,29785012}	Inadequate	\N	TPMT*12 is assigned uncertain function based on inadequate evidence. Patients genotyped TPMT*1/*12 exhibited TPMT enzymatic activity that is comparable to TPMT*1/*1 patients and there was no difference in 6-MP dose intensity between TPMT*1/*12 and TPMT*1/*1 patients (27564568). In vitro studies using mammalian cell expression systems found that TPMT.12 protein expression is decreased, enzymatic activity is decreased >50%, and TPMT.12 exhibited decreased affinity for 6-TG and SAM compared to TPMT.1 (16220112, 18708949). TPMT.12 also exhibited an increased rate of protein degradation compared to TPMT.1 (16220112). TPMT.12 enzymatic activity is decreased by 75% compared to TPMT.1 in yeast cells (13679074). An additional in vitro study found that TPMT.12 protein abundance in mammalian cells was comparable to TPMT.1 (29785012). Four out of ten variant effect predictors tested by CPIC staff predict that the TPMT*12-defining SNV, c.374C>T (p.S125L), impairs protein function.	{"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
778017	390	CYP2D6	*42	\N	No function	\N	0.0	778016	{12811367}	Limited	\N	CYP2D6*42 is assigned no function based on limited evidence in a heterozygous subject. CYP2D6*42 has been described in subjects with CYP2D6 *17/*42 genotype demonstrating decreased metabolism and a subject with CYP2D6 *40/*42 genotype demonstrating poor metabolism with a dextromethorphan substrate (12811367). CYP2D6*42 is defined by a base pair insertion resulting in a frameshift 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": 0.0, "Oceanian": null, "East Asian": 0.0, "Near Eastern": 0.0, "Central/South Asian": 0.00077314815, "Sub-Saharan African": 0.001, "African American/Afro-Caribbean": 0.0036646896}	f
779505	372	UGT1A1	*80+*37	\N	Decreased function	\N	\N	779504	{21309756,19414484,22085899,19419973}	\N	UGT1A1*80 is in very high linkage disequilibrium with *28 and *37. However, the function of the *80 allele alone, in the absence of *28 or *37, is uncertain. If a patient is only tested for *80, decreased function may be inferred.	\N	{"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
6481271	36	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 ten variant effect predictors tested by CPIC staff predict that c.321C>A (p.H107Q) impairs protein function	\N	f
777675	394	CYP2C9	*4	Decreased function	Decreased function	\N	0.5	777674	{23752738,21228733}	Limited	\N	CYP2C9*4 is assigned decreased function based on limited evidence in heterozygous patients and in vitro studies. One patient on a stable dose of warfarin with CYP2C9*1/*4 genotype required a lower weekly warfarin dose compared to CYP2C9*1/*1 patients (21228733). In an in vitro study CYP2C9*4 demonstrated 16% enzyme activity with a warfarin substrate and 22% enzyme activity with a tolbutamide substrate compared to wildtype. The CYP2C9*4 defining SNP occurs in the substrate recognition site which likely contributes to the loss of enzyme activity (23752738). 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": null, "East Asian": 0.0, "Near Eastern": 0.0011754684, "Central/South Asian": 0.0, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.0}	f
777979	390	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
778137	389	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
778370	377	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
778935	346	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
779155	373	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
3685789	185	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
3685483	185	RYR1	c.3527C>T	Variant of uncertain significance	Uncertain function	\N	n/a	3685482	{35849058}	\N	\N	BP4	{"Latino": null, "American": null, "European": null, "East Asian": null, "Near Eastern": null, "Central/South Asian": 0.0006219, "Sub-Saharan African": null}	f
3685765	185	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
3685819	185	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
779445	372	TPMT	*25	\N	No function	\N	\N	779444	{18602085}	Moderate	\N	TPMT*25 is assigned no function based on moderate evidence. Erythrocytes from individuals genotyped TPMT*1/*25 exhibited intermediate enzymatic activity (18602085). An in vitro study using a yeast expression system found that TPMT.25 exhibited decreased affinity for 6-TG and TPMT.25 enzymatic activity is decreased by 30% compared to TPMT.1 (18602085). Seven out of ten variant effect predictors tested by CPIC staff predict that the TPMT*25-defining SNV, c.634T>C (p.C212R), impairs protein function.	{"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
779219	373	RYR1	c.7372C>T	Likely Pathogenic	Malignant Hyperthermia associated	\N	n/a	779218	{33767344}	\N	\N	PS3_Mod, PS4_Mod, PM1_Sup, PM5, PP3_Mod	{"Latino": null, "American": null, "European": 0.0000147, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
778061	390	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
779223	373	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
778492	375	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
1357092	355	SLCO1B1	*48	\N	No function	\N	\N	1357091	{22232210}	Limited	\N	SLCO1B1*48 is assigned no function due to evidence supporting a full gene deletion (22232210). Therefore, consensus among experts was no function due to limited 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
779425	372	TPMT	*15	\N	No function	\N	\N	779424	{15083071,31005613}	Limited	\N	TPMT*15 is assigned no function based on limited evidence. Erythrocytes from a patient genotyped TPMT*3A/*15 exhibited very low enzymatic activity (15083071, 31005613). The patient's mother was genotyped TPMT*1/*15 and exhibited intermediate enzymatic activity (15083071). The TPMT*15-defining SNV, c.495-1G>A, disrupts the canonical splice site and results in the loss of exon 7, which is further supported by SpliceAI predictions. Additionally, the variant effect predictors, CADD and PhD-SNPg, predict that c.495-1G>A impairs protein function.	{"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
6481243	36	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, Nine out of ten 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
777975	390	CYP2D6	*21	\N	No function	\N	0.0	777974	{10471060,15618746}	Limited	\N	CYP2D6*21 is assigned no function based on limited evidence. CYP2D6*21 has been described in subjects demonstrating markedly decreased metabolism of debrisoquine and dextromethorphan (10471060, 15618746). CYP2D6*21 is defined by a base insertion resulting in a frameshift and premature stop codon, yielding a truncated and 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": null, "American": 0.0, "European": 0.0, "Oceanian": null, "East Asian": 0.0035356972, "Near Eastern": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": 0.0, "African American/Afro-Caribbean": 0.0}	f
778388	377	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
778957	346	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
778687	346	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
778691	346	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
778765	346	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
3685359	185	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
778893	346	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
3685711	185	RYR1	c.8026C>T	Likely Pathogenic	Malignant Hyperthermia associated	\N	n/a	3685710	{35849058}	\N	\N	PS4_Mod, PP1_St	{"Latino": null, "American": null, "European": 0.0000294, "East Asian": null, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null}	f
3685761	185	RYR1	c.9797T>C	Variant of uncertain significance	Uncertain function	\N	n/a	3685760	{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
3685771	185	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
3685933	185	RYR1	c.14509C>G	Variant of uncertain significance	Uncertain function	\N	n/a	3685932	{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
3685861	185	RYR1	c.12700G>C	Likely Pathogenic	Malignant Hyperthermia associated	\N	n/a	3685860	{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
778185	389	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
2091241	294	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
2091247	294	CYP2D6	*157	\N	Unknown function	\N	n/a	2091246	{}	No Evidence	\N	CYP2D6*157 is assigned unknown function due to no literature describing function of this allele. CYP2D6*157 is defined by the five SNPs defining the decreased function *29 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
6235906	41	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
778831	346	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
778997	346	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
778929	346	G6PD	Tomah	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778928	{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
7094209	39	MT-RNR1	m.930G>A	\N	uncertain risk of aminoglycoside-induced hearing loss	\N	\N	7094208	{18830133}	Inadequate evidence	\N	MT-RNR1 930G>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. While PMID 18830133 states that "..., 11 of the 151 sequences demonstrated an A > G transition at base position 930. Two of these patients had moderate-to-severe hearing loss." Table 3 of the article shows the G allele as the Human consensus and the 11 subjects as having the A allele. Furthermore, the guideline authors have reviewed institutional sample data and confirmed that the G allele is the reference allele. Therefore the variant is referenced as m.930G>A as of October 2025.	{"European": 0.0432228, "East Asian": 0.004054, "Near Eastern": 0.03408011, "Central/South Asian": 0.007368, "Sub-Saharan African": null}	f
3685529	185	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
777695	394	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
778099	390	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
3827879	167	MT-RNR1	m.786G>A	\N	uncertain risk of aminoglycoside-induced hearing loss	\N	\N	3827878	{23969527}	Inadequate evidence	\N	MT-RNR1 786G>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 (23969527). 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": 0.0, "Sub-Saharan African": null}	f
3685707	185	RYR1	c.7879G>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685706	{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
3685813	185	RYR1	c.11723A>T	Variant of uncertain significance	Uncertain function	\N	n/a	3685812	{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
3685863	185	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
6481241	36	NAT2	*42	\N	Uncertain function	\N	\N	6481240	{19909761}	Inadequate	\N	NAT2*42 is assigned uncertain function based on inadequate evidence. NAT2*42 is characterized by the core SNV c.622T>C (p.Y208H). Published in silico modeling predicts that c.622T>C (p.Y208H) does not alter NAT2 protein function (19909761). Three out of ten variant effect predictors tested by CPIC staff predict that c.622T>C (p.Y208H) impairs protein function. There are no in vitro or in vivo functional studies for NAT2*42	\N	f
778899	346	G6PD	Torun	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778898	{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
777725	394	CYP2C9	*29	Decreased function	Decreased function	\N	0.5	777724	{23752738,16788382,23844998,24118918,25142737,25951663,25144335,25476996,25614704,25832633,25884291,25924705,27163851,24077631}	Limited	\N	CYP2C9*29 is assigned decreased function based on limited evidence. Multiple in vitro studies found CYP2C9*29 demonstrated decreased clearance compared to wildtype (23752738, 23844998, 24118918, 25951663, 25144335, 25476996, 25832633, 25884291, 25924705, 24077631). Although two in vitro studies showed CYP2C9*29 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). Other studies, however, also showed CYP2C9*29 has similar clearance compared to wildtype (16788382, 25614704). Although the experts recognized there is conflicting evidence, the experts did not find it convincing as it was determined the activity of CYP2C9*29 toward most substrates was similar to CYP2C9*2 which definitively has decreased function. Therefore, consensus among experts was decreased function with an activity value of 0.5.	{"Latino": null, "American": null, "European": null, "Oceanian": null, "East Asian": 0.0022081658, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": null, "African American/Afro-Caribbean": null}	f
779296	373	SLCO1B1	*10	\N	Uncertain function	\N	\N	779295	{11477075,12490595}	Inadequate	\N	SLCO1B1*10 is assigned uncertain function based on in vitro studies demonstrating reduced uptake of estrone sulfate, but not of estradiol 17beta-d-glucuronide and rifampin (11477075, 12490595) 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
779688	326	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
778077	389	CYP2D6	*74	\N	Unknown function	\N	n/a	778076	{}	No Evidence	\N	CYP2D6*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": 0.0, "European": 0.0, "Oceanian": null, "East Asian": 0.0, "Near Eastern": 0.0, "Central/South Asian": 0.0, "Sub-Saharan African": 0.0013710798, "African American/Afro-Caribbean": 0.0}	f
6481219	36	NAT2	*31	Slow	Decreased function	\N	\N	6481218	{19909761,15564878}	Moderate	\N	NAT2*31 is assigned decreased function based on moderate evidence. NAT2*31 is characterized by the core SNVs c.70T>A (p.L24I) and c.341T>C (p.I114T). Published in silico modeling predicts that c.70T>A (p.L24I) does not impair NAT2 protein function (19909761). However, five out of ten variant effect predictors tested by CPIC staff predict that c.70T>A (p.L24I) impairs protein function and structure-based predictors suggest that c.70T>A (p.L24I) decreases protein stability which could lead to decreased function. c.341T>C (p.I114T, defining NAT2*5) has repeatedly shown decreased NAT2 N-acetylation activity in numerous in vivo and in vitro studies and five out of ten variant effect predictors tested by CPIC staff predict that c.341T>C (p.I114T) impairs protein function. Additionally, an 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*31 would presumably be degraded in the same manner and is assigned decreased function based on the function of c.341T>C (p.I114T). Despite this, it remains unknown whether c.70T>A has any combinatorial effects with c.341T>C.	\N	f
3685593	185	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
779199	373	RYR1	c.7042_7044delGAG	Likely Pathogenic	Malignant Hyperthermia associated	\N	n/a	779198	{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
777593	394	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
6481193	36	NAT2	*4	Rapid	Increased function	\N	\N	6481192	{9154882,8781741,28653770,8102597,30564082,15558239,7668286,2376572,1451720,10744128,22092036,1872889,8689813,20040334,9333101,17011540,22970273,16531626,15565348,9321764,9110365,11214777,31257615,29018032,24702251,24444407,15110095,27509179,11773863,20801937,16003747,21750470,23899363,9565293,9891107,9682266,24221535,22105431,8287065,27223070,8001235,8923605,10762005,8081359,35928262,28752039,17505821,21946899,16570187,15032315,18167504,17434923,33815485,18680467,19336229,15564878,7669073,11337936,12222688,17264801}	Definitive	\N	NAT2*4 is assigned increased function based on definitive evidence. The NAT gene nomenclature committee considered NAT2*4 as the reference allele for over two decades before the transfer of NAT2 allele nomenclature to PharmVar, which uses the GRCh38 (NC_000008.11) reference sequence. The NAT gene nomenclature committee has historically assigned acetylation activity to alleles as either "rapid" or "slow", classifying the reference NAT2*4 allele as "rapid". Under the CPIC allele function terminology, rapid acetylation alleles are categorized as "Increased Function". NAT2*4 has been studied for more than 25 years and numerous clinical and in vitro studies have demonstrated rapid acetylation by NAT2*4 with various substrates. Early clinical studies demonstrate rapid acetylation of caffeine metabolites in individuals homo- or heterozygous for the NAT2*4 allele (8102597, 7668286, 8923605, 9891107). Additional clinical studies demonstrate rapid acetylation by NAT2*4 using isoniazid (2376572, 9321764, 15565348) and sulfamethazine (1872889, 21946899). Individuals homo- or heterozygous for NAT2*4 metabolize hydralazine rapidly (24702251, 31257615). NAT2*4 is distinguished from NAT2*1 by the presence of the core SNV c.803G>A (p.R268K). c.803G>A (p.R268K) has not been shown experimentally to alter NAT2 acetylation activity in vitro nor in vivo. Accordingly, nine out of nine variant effect predictors tested by CPIC staff predict that c.803G>A is neutral/tolerated for protein function.	\N	f
778195	390	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
778243	220	CYP4F2	*3	\N	\N	\N	\N	778242	\N	\N	\N	\N	{"Latino": 0.25830573, "American": 0.4107687, "European": 0.27461374, "East Asian": 0.23247077, "Near Eastern": 0.35087985, "Central/South Asian": 0.40285128, "Sub-Saharan African": 0.09881758, "African American/Afro-Caribbean": 0.07623351}	f
778903	346	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
778799	346	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
777785	394	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
6481229	36	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). Ten out of ten 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 ten 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
778117	390	CYP2D6	*99	\N	No function	\N	0.0	778116	{29327975}	Limited	\N	CYP2D6*99 is assigned no function based on limited evidence. CYP2D6*99 has been described in a subject with CYP2D6*5/*99 genotype demonstrating markedly decreased metabolism compared to wildtype with dextromethorphan and venlafaxine substrates (29327975). CYP2D6*99 is defined by the same SNPs as CYP2D6*10 in addition to a SNP resulting in an amino acid substitution which disrupts enzyme activity yielding a 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": 0.0, "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
3685507	185	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
3685569	185	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
3685799	185	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
3685463	185	RYR1	c.2797G>A	Benign	Normal function	\N	n/a	3685462	{33767344}	\N	\N	BA1	{"Latino": 0.0004581, "American": null, "European": null, "East Asian": null, "Near Eastern": 0.003165, "Central/South Asian": null, "Sub-Saharan African": 0.004319}	f
7096545	22	NAT2	*66	Slow	Decreased function	\N	\N	7096544	{}	Moderate	\N	NAT2*66 is assigned decreased function based on moderate evidence. NAT2*66 is characterized by the core SNVs c.590G>A (p.R197Q), c.682C>T (p.P228S) 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.682C>T (p.P228S). One out of ten variant effect predictors tested by CPIC staff predict c.682C>T (p.P228S) 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 ten variant effect predictors tested by CPIC staff predict that c.590G>A (p.R197Q) impairs protein function. Thus, NAT2*66 is assigned decreased function based on c.590G>A. Despite this, the combinatorial effects associated with c.682C>T and c.590G>A are uncertain.	\N	f
779691	323	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
778436	375	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
778446	375	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
778749	346	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
3685983	185	RYR1	c.15060G>C	Variant of uncertain significance	Uncertain function	\N	n/a	3685982	{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
3685513	185	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
778087	390	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
778119	390	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
778368	381	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
3827885	167	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
3685533	185	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
3685539	185	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
779231	373	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
3685887	185	RYR1	c.13934G>A	Variant of uncertain significance	Uncertain function	\N	n/a	3685886	{35849058}	\N	\N	PM1_Sup	{"Latino": 0.0001314, "American": null, "European": 0.00001471, "East Asian": 0.002118, "Near Eastern": null, "Central/South Asian": null, "Sub-Saharan African": 0.00002418}	f
779427	372	TPMT	*16	\N	No function	\N	\N	779426	{18708949,15652243,15226673,33118454,32973300}	Moderate	\N	TPMT*16 is assigned no function based on moderate evidence. Erythrocytes from individuals genotyped TPMT*1/*16 exhibited intermediate enzymatic activity (15226673, 15652243, 33118454). In vitro studies found that TPMT.16 exhibited decreased affinity for 6-TG and enzymatic activity was decreased by 84% and 68% relative to TPMT.1 in mammalian (18708949) and yeast (15652243) cells, respectively. An in silico prediction model of TPMT variant functionality can predict >95% of variance when including TPMT*16 along with the most common variants TPMT*2, *3A, and *3C, compared to 70% without TPMT*16 (32973300). Five out of ten variant effect predictors tested by CPIC staff predict that the TPMT*16-defining SNV, c.488G>A (p.R163H), impairs protein function.	{"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
777795	376	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
779703	322	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
779744	322	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
6235916	41	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
778354	381	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
778811	346	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
6355336	39	CFTR	R75Q	\N	ivacaftor responsive	\N	\N	6355335	{}	\N	\N	\N	\N	f
778107	390	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
1103380	296	CYP2D6	*147	\N	Uncertain function	\N	n/a	1103379	{}	Inadequate	\N	CYP2D6*147 is assigned uncertain function due to inadequate evidence. CYP2D6*147 is defined by the insertion of three amino acids found in CYP2D6*30 (for which the function is uncertain) and the 100C>T variant which has been shown to cause severely decreased function of 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
3685835	185	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
778975	346	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
7096543	22	NAT2	*65	\N	Unknown function	\N	\N	7096542	{}	No evidence	\N	NAT2*65 is assigned unknown function based on a lack of evidence. NAT2*65 is characterized by the core SNVs c.613A>T (p.M205L) 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.613A>T (p.M205L). Ten out of ten variant effect predictors tested by CPIC staff predict that c.613A>T (p.M205L) is neutral for protein function.	\N	f
6355332	39	CFTR	Q1291R	\N	ivacaftor responsive	\N	\N	6355331	{}	\N	\N	\N	\N	f
6355330	39	CFTR	Q359R	\N	ivacaftor responsive	\N	\N	6355329	{}	\N	\N	\N	\N	f
6355340	39	CFTR	R117G	\N	ivacaftor responsive	\N	\N	6355339	{}	\N	\N	\N	\N	f
2899153	183	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
777677	394	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
778763	346	G6PD	Cairo	II/Deficient	II/Deficient	\N	\N	778762	{22293322,1945893,22770933}	Moderate	\N	WHO Class II assigned based on evidence supporting decreased enzyme activity (less than A-). Additionally, analysis of the clinical presentation of the 11 children with G6PD Cairo revealed that all suffered hemolytic crises due to fava bean consumption and reported varying levels of jaundice at birth. The resulting in a WHO class II assignment (22770933).	{"Latino": 0.0, "European": 0.0, "East Asian": 0.0, "Central/South Asian": 0.0, "African American/Afro-Caribbean": 0.0}	f
778821	346	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
7096547	22	NAT2	*67	Slow	Decreased function	\N	\N	7096546	{29273096}	Moderate	\N	NAT2*67 is assigned decreased function based on moderate evidence. NAT2*67 is characterized by the core SNVs c.590G>A (p.R197Q), c.803G>A (p.R268K), and c.823T>A (p.L275M). 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.823T>A (p.L275M). Five out of ten variant effect predictors tested by CPIC staff predict c.823T>A (p.L275M) 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 ten variant effect predictors tested by CPIC staff predict that c.590G>A (p.R197Q) impairs protein function. Thus, NAT2*67 is assigned decreased function based on c.590G>A. Despite this, the combinatorial effects associated with c.823T>A and c.590G>A are uncertain.	\N	f
3685857	185	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
777447	394	CYP2B6	*13	No function	No function	\N	\N	777446	{15190123,17559344,20517174,30201214}	Limited	\N	CYP2B6*13 (c.415A>G, p.K139E; c.516G>T, p.Q172H/splice defect; c.785A>G, p.K262R) - No function: CYP2B6*13 is assigned no function. CYP2B6*13 contains the same variants as CYP2B6*6, which is assigned decreased function, and CYP2B6*8 which is assigned no function. Most in vitro studies including those using cDNA expression systems (15190123, 20517174, 30201214) and human liver microsomes (17559344) found that CYP2B6*13 has no enzyme activity; only one in vitro study using a cDNA expression system showed residual activity for artemether metabolism compared to the *1 reference. This discrepancy is probably due to differences in the in vitro expression systems and substrates used. 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
777589	394	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
777691	394	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
778406	377	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
778400	377	DPYD	c.1371C>T	Normal function	Normal function	\N	1.0	778399	{23588312}	Limited	\N	5-fluorouracil (ex vivo)	{"Latino": 0.00071320933, "European": 0.00017700421, "East Asian": 0.0, "Central/South Asian": 0.00008935568, "Sub-Saharan African": 0.020694444, "African American/Afro-Caribbean": 0.015828025}	f
778859	346	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
778945	346	G6PD	Krakow	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778944	{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
779027	346	G6PD	Laibin	Uncertain	Uncertain function	\N	\N	779026	{22293322,17018380}	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
778825	346	G6PD	North Dallas	I/Deficient with CNSHA	I/Deficient with CNSHA	\N	\N	778824	{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
778683	346	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
3685393	185	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
2899155	183	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
777535	394	CYP2C19	*2	\N	No function	\N	\N	777534	{8195181,22027650}	Definitve	\N	CYP2C19*2 is assigned no function based on definitive evidence. CYP2C19*2 has been studied for more than 20 years and its association with impaired function is well-established (8195181, 22027650). CYP2C19*2 is defined by splicing defects resulting in a truncated protein lacking a heme binding region, making it a nonfunctional protein. CYP2C19*2 was first identified in a homozygous subject demonstrating decreased mephenytoin metabolism and was subsequently identified in seventeen additional subjects demonstrating decreased mephenytoin metabolism (8195181). Therefore, consensus among experts was no function based on definitive evidence.	{"Latino": 0.104187496, "American": 0.121365316, "European": 0.14685704, "Oceanian": 0.6095202, "East Asian": 0.28352264, "Near Eastern": 0.11984708, "Central/South Asian": 0.269916, "Sub-Saharan African": 0.15684253, "African American/Afro-Caribbean": 0.18149492}	f
777721	394	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
778442	375	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
3685521	185	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
779177	373	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
3685443	185	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
777553	394	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
778079	390	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
778121	390	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
778159	390	CYP2D6	*120	\N	No function	\N	0.0	778158	{}	Limited	\N	CYP2D6*120 is assigned no function based on limited evidence. CYP2D6*120 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
2955640	215	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
777431	394	CYP2B6	*5	Normal function	Normal function	\N	\N	777430	{11470993,12642465,17559344,20662624,20841522,21659470,22354160,23254426,23399569,23990572,25897175,26389554,26655325,31324697,32238417}	Strong	\N	CYP2B6*5 (c.1459C>T, p.R487C) - Normal function: CYP2B6*5 is assigned normal function based on in vivo (heterozygous and homozygous patients) and in vitro studies. Multiple studies evaluating efavirenz plasma concentrations among patients with HIV found that carriers of the CYP2B6*5 allele had similar efavirenz plasma concentrations compared to the *1 reference (20662624, 20841522, 22354160, 23254426, 23399569, 23990572). A study evaluating efavirenz content in hair samples among HIV patients taking efavirenz for more than three months found that the CYP2B6*5 allele did not impact long term efavirenz exposure (26655325). In human liver microsomes, decreased protein expression and/or activity was reported (11470993, 17559344). In in vitro expression systems, activity ranged from decreased (32238417, 31324697) to no change (21659470) and increased (12642465, 25897175) activity compared to the *1 reference with various substrates. Since differences in protein expression and enzyme activity observed in vitro were not reflected by meaningful differences in vivo in numerous clinical studies (20662624, 20841522, 22354160, 23254426, 23399569, 23990572, 26389554), consensus among experts was normal function based on strong evidence.	{"Latino": 0.038105432, "European": 0.11547839, "Oceanian": 0.02, "East Asian": 0.011, "Near Eastern": 0.024, "Central/South Asian": null, "Sub-Saharan African": 0.02, "African American/Afro-Caribbean": 0.062061857}	f
777443	394	CYP2B6	*11	Decreased function	Uncertain function	\N	\N	777442	{15190123,19916993,20517174,21746968,23734829,23778320,25303294,26779253,27045425,30201214,28886044}	Limited	\N	CYP2B6*11 (c.136A>G, p.M46V) – Uncertain function: CYP2B6*11 is assigned uncertain function. In vitro studies using cDNA expression systems demonstrated decreased or no enzyme activity compared to the *1 reference (20517174, 21746968, 15190123, 30201214). Some studies with heterozygous and homozygous CYP2B6*11 patients showed that this allele is associated with increased exposure of efavirenz (27045425, 26779253, 28886044), while other clinical studies (25303294, 23734829, 19916993, 23778320) did not consistently demonstrate decreased enzyme activity or altered PK with efavirenz. Therefore, consensus among experts was uncertain function based on consistent in vitro data but limited and inconsistent clinical evidence.	{"Latino": 0.0016810922, "European": 0.0030138378, "Oceanian": null, "East Asian": 0.0, "Near Eastern": null, "Central/South Asian": 0.0021935336, "Sub-Saharan African": 0.070927635, "African American/Afro-Caribbean": 0.0024664723}	f
2899159	183	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
779397	372	TPMT	*3A	\N	No function	\N	\N	779396	{16220112,9177237,9103127,18708949,8644731,8561894,15967990,9246020,9931346,15226673,23252716,31005613,11304783,10580024,19057372,33205673,23585236,29387964,33928426}	Definitive	\N	TPMT*3A is assigned no function based on definitive evidence. Erythrocytes from individuals heterozygous for TPMT*3A exhibited intermediate enzymatic activity, while erythrocytes from individuals homozygous for TPMT*3A or heterozygous for TPMT*3A in combination with another no function allele exhibited low enzymatic activity (9103127, 9246020, 9931346, 15226673, 23252716, 31005613). Patients carrying TPMT*3A alleles exhibited increased plasma concentrations of TGNs, decreased plasma concentrations of methylated metabolites, and tolerate lower doses of thiopurines (10580024, 11304783, 19057372, 23585236, 29387964, 33205673, 33928426). In vitro studies found that TPMT.3A protein expression and enzymatic activity is substantially decreased or undetectable relative to TPMT.1 in yeast cells (8644731, 9177237), mammalian cells (16220112,18708949, 8561894), and patient erythrocytes (9177237, 8644731, 8561894). Loss of TPMT.3A protein expression is attributed to rapid degradation by the proteasome (16220112, 9177237, 15967990). Seven and eight out of ten variant effect predictors tested by CPIC staff predict that the TPMT*3A-defining SNVs, c.460G>A (p.A154T) and c.719A>G (p.Y240C), impair protein function, respectively.	{"Latino": 0.041727107, "European": 0.033840433, "East Asian": 0.00030599828, "Near Eastern": 0.0130693065, "Central/South Asian": 0.0042245653, "Sub-Saharan African": 0.0016235898, "African American/Afro-Caribbean": 0.008}	f
1932994	136	CYP2C9	*80	\N	\N	\N	\N	1932993	\N	\N	\N	\N	\N	f
777453	394	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
778420	377	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
778438	375	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
1002686	366	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
779423	372	TPMT	*14	\N	No function	\N	\N	779422	{18708949,15083071,31005613}	Moderate	\N	TPMT*14 is assigned no function based on moderate evidence. Erythrocytes from individuals genotyped TPMT*3A/*14 and TPMT*1/*14 exhibited very low and intermediate enzymatic activity, respectively (15083071, 31005613). An in vitro study using a mammalian cell expression system found that TPMT.14 protein expression and enzymatic activity are undetectable in cells (18708949). Four out of eight variant effect predictors tested by CPIC staff predict that the TPMT*14-defining SNV, c.1A>G (p.M1V), impairs protein function. c.1A>G (p.M1V) is predicted to disrupt protein translation due to the loss of the canonical start codon, and there is no alternative start codon available	{"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
777457	394	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
777471	394	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
