Numerous RyR1 and RyR2 mutations associated with MH and CPVT, respectively, have been functionally characterized with the vast majority resulting in gain-of-function channels (Hernandez-Ochoa et al., 2016; Fowler and Zissimopoulos, 2022). This evidence concerns the gene RYR1 and catecholaminergic polymorphic ventricular tachycardia.