ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.7373G>A (p.Arg2458His) (rs121918594)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PharmGKB RCV000786580 SCV000925402 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 RCV000786645 SCV000925467 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 RCV000786646 SCV000925468 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 RCV000786647 SCV000925469 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 RCV000786648 SCV000925470 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 RCV000786649 SCV000925471 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 RCV000786650 SCV000925472 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.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000079164 SCV000230705 pathogenic not provided 2013-10-18 criteria provided, single submitter clinical testing
Invitae RCV000793289 SCV000932637 pathogenic RYR1-Related Disorders 2018-10-11 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 2458 of the RYR1 protein (p.Arg2458His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs121918594, ExAC 0.01%). This variant has been reported to segregate with autosomal dominant malignant hyperthemia in several families (PMID:19648156) and has been reported in many individuals affected with malignant hyperthermia (PMID:9450902, 22415532, 16732084, 18564801, 12700608). This variant has also been observed in combination with another RYR1 variant in individuals affected with arthrogryposis multiplex congenita (PMID:24319099). ClinVar contains an entry for this variant (Variation ID: 12972). Experimental studies have shown that this missense change alters protein function in vitro (PMID:27586648, 9334205, 9873004, 12732639). This missense change is located in a region of the RYR1 protein where a significant number of previously reported RYR1 missense mutations are found (PMID: 16084090). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000013839 SCV000034086 risk factor Malignant hyperthermia, susceptibility to, 1 1998-01-01 no assertion criteria provided literature only
Leiden Muscular Dystrophy (RYR1) RCV000079164 SCV000154619 not provided not provided no assertion provided not provided

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