Low-frequency variants at the locus among Puerto Rican patients on warfarin: predictions of functionality and conservation.

Perform predictions of functional consequences of variants identified by next-generation sequencing in Puerto Ricans. Identified low-frequency variants (minor allele frequencies <2%) were evaluated using the Combined Annotation-Dependent Depletion (CADD v1.3) tools and molecular modeling/docking analysis to predict impact on CYP2C9 activity. ,,,, and a novel induce conformational changes that affect the binding site of -warfarin. Most of these deleterious variants occur at higher frequency among individuals with large African ancestry. The unfavorable distance of -warfarin from heme group, and low-binding interactions due to these variants, suggest major complications during warfarin therapy. This study contributes to the field by predicting functional alterations of rare variants for the first time in Hispanics.