Functional Annotation Of Kcnq1 Variants Of Unknown Significance Using Automated Electrophysiology

Channelopathies result from ion channel dysfunction caused by mutation in either pore-forming subunits or regulatory proteins. The widespread use of genetic and genomic testing has led to an explosive growth in the number of newly discovered ion channel variants associated with human diseases and in reference populations. For example, in congenital long QT syndrome (LQTS), hundreds of variants have been discovered in KCNQ1 and KCNE1, which encode the pore-forming subunit and accessory protein required to generate the slow delayed cardiac rectifier current (IKs).