Evolutionary coupling analysis guides identification of mistrafficking-sensitive variants in cardiac K channels: Validation with hERG.

Loss of function (LOF) mutations of voltage sensitive K channel proteins hERG (Kv11.1) and KCNQ1 (Kv7.1) account for the majority of instances of congenital Long QT Syndrome (cLQTS) with the dominant molecular phenotype being a mistrafficking one resulting from protein misfolding.