Until the first human missense variant was discovered in 2012, and linked to a severe cardiac arrhythmia (Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)) and sudden cardiac death (SCD) (Nyegaard et al., 2012), mutations in the CALM genes were considered incompatible with life (Jensen et al., 2018). This evidence concerns the gene CALM2 and cardiac rhythm disease.