ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.6502G>A (p.Val2168Met) (rs118192176)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics,Klinikum rechts der Isar RCV000578323 SCV000680358 pathogenic Minicore myopathy 2017-11-15 criteria provided, single submitter clinical testing
Invitae RCV000557804 SCV000659996 pathogenic RYR1-Related Disorders 2018-12-31 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 2168 of the RYR1 protein (p.Val2168Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. This variant is not present in population databases (rs118192176, ExAC no frequency). This variant has been reported to segregate with malignant hyperthermia (MH) in a single family (PMID: 9497245), in several individuals affected with MH, and is considered one of most common MH mutations in the European population (PMID: 25466363, 9497245, 19648156, 11668625). ClinVar contains an entry for this variant (Variation ID: 12976). This sequence change is located in a region of the RYR1 protein where a significant number of previously reported RYR1 missense mutations are found (PMID: 16084090). In vitro contracture test (IVCT) studies have shown that this missense change results in an increase in sensitivity to halothane (PMID: 11668625). For these reasons, this variant has been classified as Pathogenic.
Leiden Muscular Dystrophy (RYR1) RCV000119656 SCV000154563 not provided not provided no assertion provided not provided
OMIM RCV000013845 SCV000034092 risk factor Malignant hyperthermia, susceptibility to, 1 1998-03-01 no assertion criteria provided literature only
PharmGKB RCV000786463 SCV000925285 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 RCV000786464 SCV000925286 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 RCV000786465 SCV000925287 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 RCV000786466 SCV000925288 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 RCV000786565 SCV000925387 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 RCV000786566 SCV000925388 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 RCV000786567 SCV000925389 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 RCV000119656 SCV000852713 pathogenic not provided 2017-09-27 criteria provided, single submitter clinical testing

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