19825159: positive in vitro contracture test (biopsied muscle strips) (IVCT); 28259615: positive IVCT; 22547813: R174W mutation does not alter the voltage dependence of EC coupling, indicating that this mutation does not shift the equilibrium of RyR1 toward the activated state. R174W mutation alters the resting conformation of CACNA1S such that it no longer suppresses resting calcium leak via RYR1 and R174W mutation also serves to amplify this resting leak. R174W mutation disrupts the ability of CACNA1S to repress resting calcium leak from SR via RYR1 leading t elevated resting myoplasmic calcium and increased sensitivity to MH triggers