For certain gene-disease pairs, there are gene regions where there is a higher confidence for pathogenicity such as, for non-truncating variants, the transmembrane regions and C-terminus domains for KCNQ1-related LQTS [38, 39], and the ion channel transmembrane regions and specific N-terminus and C-terminus domains for KCNH2-related LQTS [39]. Here, KCNQ1 is linked to familial long QT syndrome.