Location of arrhythmia-associated mutations (AAMs) and non-synonymous single nucleotide polymorphisms (nsSNPs) in human HERG and KCNQ1 subunits. a) Schematic of the human HERG subunit. Included are 172 AAMs at 134 sites and 16 nsSNPs at 16 sites. b) Schematic of KCNQ1 subunit. Included are 174 disease mutations at 130 sites and 12 nsSNPs at 12 sites. Blue region = voltage sensing domain (S1–S4), pink region = pore forming domain (S5–S6), yellow = PAS domain or CNBD domain in cytosolic regions of the channel. Red X's delimit the region used in analysis. Circles: red = 1 AAMs, yellow = 2 mutations/site, green = 3 mutations/site, blue = 4 mutations/site, purple = 5 mutations/site, blue outline = 1 nsSNP/site, green outline = overlap of disease mutation and evolutionary change, red outline = overlap of AAM, evolutionary change and nsSNP.