The RYR2 gene encodes the cardiac ryanodine receptor that regulates contraction by the intracellular release of calcium and plays and essential rolein excitation-contraction in the heart (PMID: 24743769) . Pathogenic changes that result in gain-of-function of the RYR2 gene have reported in individuals with several types of tachyarrhythmias, including catecholaminergic polymorphic ventricular tachycardia (CPVT), catecholaminergic idiopathic ventricular fibrillation, atrial fibrillation and a structurally normal heart (Napolitano et al., 2014). Loss of function variants have not been associated with RYR2-related disorders. An in-frame deletion of exon 3 has been reported in patients with CPVT and other arrhythmias, however the pathogenetic mechanism has not been well defined (PMID: 24743769).