Amino-acid level signal-to-noise variant frequency for the three major gene products associated with LQTS. Frequency of LQTS (green) and WES (blue) cohort variant frequency versus amino acid position for Kv7.1 (A), Kv11.1 (B), and Nav1.5 (C). AKAP9, AKAP9-protein binding; CD, cytoplasmic; cNBD, C-terminal nucleotide binding; FGF, FGF13 binding; G, inactivation gate; KCNE1, KCNE1-protein binding; LC, L-type Ca2+ channel binding; PAS, Per-Arnt-Sim; SF, selectivity filter; S1–S6, transmembrane; SSTK, SSTK-interacting protein; TM, transmembrane; TSSK6-activating co-chaperone protein binding domains.