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Updated: Jan 19, 2026
Functional Characterization of Endogenously Expressed Human RYR1 Variants
Published on: June 9, 2021
Bayesian modeling to predict malignant hyperthermia susceptibility and pathogenicity of RYR1, CACNA1S and STAC3
Senthilkumar Sadhasivam1, Barbara W Brandom2, Richard A Henker2
1Department of Anesthesia, Riley Hospital for Children at Indiana University Health, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Abstract:
Aim: Identify variants in RYR1, CACNA1S and STAC3, and predict malignant hyperthermia (MH) pathogenicity using Bayesian statistics in individuals clinically treated as MH susceptible (MHS). Materials & methods: Whole exome sequencing including RYR1, CACNA1S and STAC3 performed on 64 subjects with: MHS; suspected MH event or first-degree relative; and MH negative. Variant pathogenicity was estimated using in silico analysis, allele frequency and prior data to calculate Bayesian posterior probabilities. Results: Bayesian statistics predicted CACNA1S variant p.Thr1009Lys and RYR1 variants p.Ser1728Phe and p.Leu4824Pro are likely pathogenic, and novel STAC3 variant p.Met187Thr has uncertain significance. Nearly a third of MHS subjects had only benign variants. Conclusion: Bayesian method provides new approach to predict MH pathogenicity of genetic variants.
