Sadhasivam, SenthilkumarHenker, Richard A.Brandom, Barbara W.McAuliffe, John J.2021-05-282021-05-282019-09-27Sadhasivam, S., Brandom, B. W., Henker, R. A., & McAuliffe, J. J. (2019). Bayesian modeling to predict malignant hyperthermia susceptibility and pathogenicity of RYR1, CACNA1S and STAC3 variants. Pharmacogenomics, 20(14), 989–1003. https://doi.org/10.2217/pgs-2019-00551462-2416https://hdl.handle.net/1805/26071Aim: 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.en-USCACNA1Scontracture testexomegeneticmalignant hyperthermiamusclenext-generation sequencingnovelpathologicRYR1STAC3Article