CALM3 and catecholaminergic polymorphic ventricular tachycardia: CPVT is caused by genetically encoded abnormalities in cardiomyocyte proteins fundamental to cardiomyocyte calcium homeostasis, most commonly in RyR2 and associated proteins calsequestrin (CASQ2), calmodulin (CALM), and TRDN. Approximately 60% to 70% of patients with a definitive clinical diagnosis of CPVT will have identifiable variants in RyR2, with most located in one of the following four highly conserved, functionally important domains of the gene: domain I AA 57-466, domain II 2246-2534, domain III 3778-4201, and domain IV 4497-4959 (Figure 4).