Our findings suggested that most silent or missense mutations may not significantly compromise RYR protein function, because no key mutations were found in known RYR-related diseases, such as catecholaminergic polymorphic ventricular tachycardia (CPVT) (RYR2) or malignant hyperthermia (RYR1)6, 7, indicating that they may not lead to serious phenotypes observed in muscle and heart diseases. This evidence concerns the gene RYR1 and heart disorder.