Partial restoration of the long QT syndrome associated KCNQ1 A341V mutant by the KCNE1 β-subunit

► KCNE1 functionally restored a long QT syndrome-associated A341V mutant. ► The resultant A341V + KCNE1 current had distinct biophysical characteristics. ► A341V had a dominant negative effect on channel current. ► Heterozygous expression of A341V + KCNQ1 + KCNE1 altered cardiac excitability in a computational model of ventricular action potentials. ► These changes contribute to the severe clinical phenotype of carriers of A341V.