Comprehensive functional evaluation of KCNE1 variants using automated patch clamp recording

Abstract

KCNE1 is a single transmembrane accessory protein that co-assembles with the voltage-gated potassium channel KCNQ1 (Kv7.1) to form the IKs channel complex critical for cardiac repolarization. Pathogenic variants in KCNE1 are associated with congenital long-QT syndrome (LQTS) type 5 and hearing loss. The pathogenicity of KCNE1 variants can be determined by assessing their functional consequences in heterologous cells by co-expressing KCNQ1. In this study, we performed functional analyses of all LQTS-associated variants reported in the literature and rare coding variants identify by exome sequencing of diverse populations (source: gnomAD database) using automated patch clamp recording.