ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.6487C>T (p.Arg2163Cys) (rs118192175)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PharmGKB RCV000786456 SCV000925278 drug response desflurane response - Toxicity/ADR reviewed by expert panel curation PharmGKB Level of Evidence 1A: Annotation for a variant-drug combination in a CPIC or medical society-endorsed PGx guideline, or implemented at a PGRN site or in another major health system.
PharmGKB RCV000786457 SCV000925279 drug response enflurane response - Toxicity/ADR reviewed by expert panel curation PharmGKB Level of Evidence 1A: Annotation for a variant-drug combination in a CPIC or medical society-endorsed PGx guideline, or implemented at a PGRN site or in another major health system.
PharmGKB RCV000786458 SCV000925280 drug response halothane response - Toxicity/ADR reviewed by expert panel curation PharmGKB Level of Evidence 1A: Annotation for a variant-drug combination in a CPIC or medical society-endorsed PGx guideline, or implemented at a PGRN site or in another major health system.
PharmGKB RCV000786459 SCV000925281 drug response isoflurane response - Toxicity/ADR reviewed by expert panel curation PharmGKB Level of Evidence 1A: Annotation for a variant-drug combination in a CPIC or medical society-endorsed PGx guideline, or implemented at a PGRN site or in another major health system.
PharmGKB RCV000786460 SCV000925282 drug response methoxyflurane response - Toxicity/ADR reviewed by expert panel curation PharmGKB Level of Evidence 1A: Annotation for a variant-drug combination in a CPIC or medical society-endorsed PGx guideline, or implemented at a PGRN site or in another major health system.
PharmGKB RCV000786461 SCV000925283 drug response sevoflurane response - Toxicity/ADR reviewed by expert panel curation PharmGKB Level of Evidence 1A: Annotation for a variant-drug combination in a CPIC or medical society-endorsed PGx guideline, or implemented at a PGRN site or in another major health system.
PharmGKB RCV000786462 SCV000925284 drug response succinylcholine response - Toxicity/ADR reviewed by expert panel curation PharmGKB Level of Evidence 1A: Annotation for a variant-drug combination in a CPIC or medical society-endorsed PGx guideline, or implemented at a PGRN site or in another major health system.
GeneDx RCV000119653 SCV000567329 pathogenic not provided 2018-01-24 criteria provided, single submitter clinical testing The R2163C pathogenic variant in the RYR1 gene has been reported in multiple individuals inassociation with malignant hyperthermia (Manning et al., 1998). Functional studies of this variant incultured cells indicate that resting calcium concentration is unchanged from wildtype RYR1 (Tong etal., 1999), but studies in dyspedic myotubes indicate that the R2163C variant leads to heightenedsensitivity to depolorization and direct channel agonists (Yang et al., 2003). R2163C was not observedin approximately 6500 individuals of European and African American ancestry in the NHLBI ExomeSequencing Project, indicating it is not a common benign variant in these populations. The R2163Cvariant is a non-conservative amino acid substitution, which occurs at a position that is conservedacross species. In silico analysis predicts this variant is probably damaging to the proteinstructure/function. Pathogenic missense variants in the same (R2163P, R2163H) and nearby (G2160S,V2168M) residues have been reported in the Human Gene Mutation Database in association withRYR1-related disorders (Stenson et al., 2014), supporting the functional importance of this region ofthe protein. We interpret R2163C as a pathogenic variant.
PreventionGenetics,PreventionGenetics RCV000119653 SCV000852709 pathogenic not provided 2016-06-27 criteria provided, single submitter clinical testing
OMIM RCV000013840 SCV000034087 risk factor Malignant hyperthermia, susceptibility to, 1 1998-03-01 no assertion criteria provided literature only
GeneReviews RCV000056223 SCV000087312 pathologic Myopathy, Central Core 2010-05-11 no assertion criteria provided curation Converted during submission to Pathogenic.
Leiden Muscular Dystrophy (RYR1) RCV000119653 SCV000154560 not provided not provided no assertion provided not provided

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