Rare, non-truncating RYR2 variants detected in 1200 referral cases and 155 well-phenotyped CPVT cases were used to define three case-enriched clusters in RYR2 (residues 2138–2538, 3935–4196 and 4721–4959), partially overlapping with previously identified disease hotspots (Fig. 5). The gene discussed is RYR2; the disease is catecholaminergic polymorphic ventricular tachycardia.