ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.6488G>A (p.Arg2163His) (rs118192163)

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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000119654 SCV000589650 likely pathogenic not provided 2015-11-09 criteria provided, single submitter clinical testing The R2163H likely pathogenic variant in the RYR1 gene has been reported in association with malignant hyperthermia and central core disease (Manning et al., 1998; Robinson et al., 2002). Functional studies indicate that the R163H variant is more sensitive to calcium- and halothane-induced intracellular calcium release when compared to the wild type channel (Tong et al., 1997). The R2163H variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R2163H variant is a conservative amino acid substitution, which occurs within the 6 X approximate repeats region and within the cytoplasmic topo domain at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants in the same and in nearby residues (G2160S, R2163P, R2163C, V2168M, I2182F) have been reported in the Human Gene Mutation Database in association with RYR1-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein. The R2163H variant is a strong candidate for a pathogenic variant. However the possibility it may be a rare benign variant cannot be excluded
GeneReviews RCV000013842 SCV000087313 pathologic Myopathy, Central Core 2010-05-11 no assertion criteria provided curation Converted during submission to Pathogenic.
Leiden Muscular Dystrophy (RYR1) RCV000119654 SCV000154561 not provided not provided no assertion provided not provided
OMIM RCV000013841 SCV000034088 risk factor Malignant hyperthermia, susceptibility to, 1 1998-03-01 no assertion criteria provided literature only
OMIM RCV000013842 SCV000034089 pathogenic Myopathy, Central Core 1998-03-01 no assertion criteria provided literature only
PharmGKB RCV000786558 SCV000925380 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 RCV000786559 SCV000925381 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 RCV000786560 SCV000925382 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 RCV000786561 SCV000925383 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 RCV000786562 SCV000925384 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 RCV000786563 SCV000925385 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 RCV000786564 SCV000925386 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.
PreventionGenetics RCV000119654 SCV000852710 pathogenic not provided 2013-11-20 criteria provided, single submitter clinical testing

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