RYR1 and skeletal muscle disorder: Additionally, mutations in the RYR1 gene led to some skeletal muscle disorders and multiple diseases that are characterized by malignant hyperthermia and central core disease belonging to congenital disease. RYR1 variants are presented to influence RYR1 Ca2+release that led to sarcoplasmic reticulum Ca2+ leak and Ca2+ depletion, which causes muscle weakness [20].