There are instances where evidence for disease comes primarily from one variant class such as missense variants only in MYL2, MYL3, and TPM1-related HCM, or from a single well-characterised variant, such as TMEM43-related ARVC and the founder missense variant NM_024334.3(TMEM43) c.1073C>T (p.S358L) [35]. The gene discussed is MYL2; the disease is Arrhythmogenic right ventricular dysplasia.