ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.7304G>A (p.Arg2435His) (rs28933396)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000707405 SCV000836503 pathogenic RYR1-Related Disorders 2018-06-08 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 2435 of the RYR1 protein (p.Arg2435His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to segregate with malignant hyperthemia and/or central core disease in several families (PMID:8220422, 19658156) and has been reported in many individuals affected with malignant hyperthermia (PMID:23842196, 21965348). ClinVar contains an entry for this variant (Variation ID: 12966). Experimental studies have shown that this missense change alters protein function in vitro (PMID:11524458, 27586648, 9873004, 9334205). 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). For these reasons, this variant has been classified as Pathogenic.
Leiden Muscular Dystrophy (RYR1) RCV000119699 SCV000154606 not provided not provided no assertion provided not provided
OMIM RCV000013832 SCV000034079 pathogenic Myopathy, Central Core 1997-02-21 no assertion criteria provided literature only
PharmGKB RCV000786617 SCV000925439 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 RCV000786618 SCV000925440 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 RCV000786619 SCV000925441 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 RCV000786620 SCV000925442 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 RCV000786677 SCV000925499 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 RCV000786678 SCV000925500 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 RCV000786679 SCV000925501 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 RCV000119699 SCV000852764 pathogenic not provided 2017-10-20 criteria provided, single submitter clinical testing

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