Heterozygous RyR2R2474S/V3599K mice showed no CPVT, in contrast to RyR2R2474S/+ mice, clearly indicating that genetic enhancement of CaM binding affinity to RyR2 by a single amino-acid substitution rescues CPVT-associated arrhythmogenesis, characterized by bidirectional or polymorphic ventricular tachycardia, spontaneous Ca2+ transients, and Ca2+ sparks17. The gene discussed is RYR2; the disease is catecholaminergic polymorphic ventricular tachycardia.