KCNQ1 and Familial short QT syndrome: For example, almost all evidence for KCNQ1 as a cause of short QT syndrome is derived from a single missense variant (NP_000209.2:p.(Val141Met)) via a gain-of-function mechanism,36 but this does not by itself inform whether other missense variants may cause disease or if LOF is also a possible mechanism of disease.