In the current study, we utilize several large published cohorts of clinically diagnosed LQTS patients and the publicly available gnomAD genetic database (gnomad.broadinstitute.org) representing over 140 000 subjects to serve as an unselected population cohort, to assess whether certain sub-domains of the KCNQ1-encoded Kv7.1 channel are more pre-disposed to host rare disease-associated missense variants. This evidence concerns the gene KCNQ1 and familial long QT syndrome.