Malignant hyperthermia associated with a variant of uncertain significance c.12146A>C (p.Glu4049Ala) in the RYR1 gene: a case report

Abstract

The authors present successful management of malignant hyperthermia crisis with CGS score 53. Molecular genetic analysis revealed a previously unreported variant c.12146A>C (p.Glu4049Ala) in the RYR1 gene that was initially classified as a variant of uncertain significance. This variant is absent in major databases (ClinVar, gnomAD, European Malignant Hyperthermia Group). Classic malignant hyperthermia crisis in carrier provides key clinical evidence for its pathogenicity and prompts re-evaluation of its baseline classification. These findings will contribute to international databases on pathogenic human variants. They are also crucial for improving the safety of anesthetic management in individuals with this genetic predisposition.