ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.7523G>A (p.Arg2508His) (rs193922818)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000528193 SCV000660028 pathogenic RYR1-Related Disorders 2018-07-17 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 2508 of the RYR1 protein (p.Arg2508His). 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 (rs193922818, ExAC no frequency). This variant has been reported in individuals affected with malignant hyperthermia, central core disease and King _x0001_Denborough syndrome (PMID: 16621918, 16732084, 16835904, 17483490, 20142353, 23558838, 25960145). This variant has also been reported to arise de novo in an individual affected with malignant hyperthermia and muscle weakness and an individual affected with central core myopathy (PMID: 17483490, 21282829). ClinVar contains an entry for this variant (Variation ID: 133207). Different missense substitutions at this codon (p.Arg2508Cys and p.Arg2508Gly) have been determined to be pathogenic (PMID: 16621918, 19685112, 26381711). This suggests that the arginine residue is critical for RYR1 protein function and that other missense substitutions at this position may also be pathogenic. Experimental studies have shown that this missense change leads to an increased sensitivity to caffeine and 4-chloro-m-cresol as compared to wildtype RYR1 (PMID: 26381711). For these reasons, this variant has been classified as Pathogenic.
Leiden Muscular Dystrophy (RYR1) RCV000119719 SCV000154626 not provided not provided no assertion provided not provided
PharmGKB RCV000786676 SCV000925498 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 RCV000786718 SCV000925540 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 RCV000786719 SCV000925541 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 RCV000786720 SCV000925542 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 RCV000786721 SCV000925543 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 RCV000786722 SCV000925544 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 RCV000786723 SCV000925545 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 RCV000119719 SCV000852781 pathogenic not provided 2017-10-20 criteria provided, single submitter clinical testing

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