Figure 1: JPH2 Mutation A405S Occurred De Novo and Affects a Conserved Residue

(A) Pedigree of HCM proband with JPH2 mutation A405S. (B) Cartoon showing that the JPH2 mutation A405S is localized within the alpha helix domain. (C) Alignment showing conservation of JPH2 sequences across species, the mutant residue is marked by the red box. HCM = hypertrophic cardiomyopathy; JPH2 = junctophilin-2; LVOTO = left ventricular outflow tract obstruction; MORN = membrane occupation and recognition nexus; PM = plasma membrane; RyR2 = ryanodine receptor type-2; SR = sarcoplasmic reticulum; TMD = transmembrane domain; VGCC = voltage-gated calcium channel.