Our data support that the D3291V-RyR2 is a loss-of-function RyR2 variant responsible for an atypical form of CPVT inducing a mild dysfunction in basal conditions but leading potentially to fatal events through its unresponsiveness to adrenergic stimulation. The gene discussed is RYR2; the disease is catecholaminergic polymorphic ventricular tachycardia.