RYR1 and Malignant hyperthermia: The large majority of the more than 100 RYR1 mutations identified to date were dominant mutations associated with malignant hyperthermia susceptibility (MHS) and central core disease (CCD) phenotypes, typically clustered in the cytoplasmic N-terminal (MHS/CCD region 1, amino acids 35 – 614; mainly MHS), the central (MHS/CCD region 2, amino acids 2163 – 2458; mainly MHS) and the C-terminal (MHS/CCD region 3, amino acids 4550 – 4940; mainly CCD) domains of the protein [for review, [48]; also [32,49]].