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