From PharmGKB
Malignant hyperthermia susceptibility (MHS) is a predisposition to a potentially life-threatening, hypermetabolic reaction triggered by potent volatile anesthetics (i.e. desflurane, enflurane, halothane, isoflurane, methoxyflurane, and sevoflurane) or the depolarizing muscle relaxant succinylcholine. These agents are relatively contraindicated in persons with MHS. MHS is diagnosed either by a positive response to the in vitro contracture test (IVCT) or the caffeine-halothane contracture test (CHCT), or by the presence of a pathogenic variant in RYR1 or CACNA1S that has been identified as causative for MHS (PMID: 30499100). Absence of pathogenetic variants in RYR1 or CACNA1S does not eliminate the chance of MHS based on findings that the genetic cause remains unknown for about half of all MH survivors, with contracture test-confirmed MHS (PMID: 28902675). Both genes are included on the list of actionable secondary findings by the American College of Medical Genetics and Genomics. MHS is inherited in an autosomal dominant manner and a positive result for a patient has familial ramifications. In addition to potential variations in RYR1 or CACNA1S, personal or family history of a reaction to these drugs or agents needs to be considered. Therapeutic guidelines for the use of potent volatile anesthetic agents and succinylcholine in the context of RYR1 or CACNA1S genotypes have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC).  https://www.pharmgkb.org/guidelineAnnotation/PA166180457