This mutation is localized in the FKBP12.6-binding domain of the RYR2 protein.38 In agreement with our findings,37 these authors showed that while in all control cardiomyocytes isoproterenol caused a positive chronotropic effect, but no arrhythmias, in 57.9% of the CPVT cardiomyocytes isoproterenol caused a negative chronotropic effect. Here, RYR2 is linked to catecholaminergic polymorphic ventricular tachycardia.