ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.1021G>A (p.Gly341Arg) (rs121918592)

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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000013836 SCV000225240 likely pathogenic Malignant hyperthermia, susceptibility to, 1 2014-09-05 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000119406 SCV000225241 likely pathogenic not provided 2014-09-05 criteria provided, single submitter clinical testing
Invitae RCV000655541 SCV000777472 pathogenic RYR1-Related Disorders 2018-04-26 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 341 of the RYR1 protein (p.Gly341Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to segregate with malignant hyperthermia in several families (PMID: 8012359, 24433488, 8825043), and has also been reported in numerous individuals affected with malignant hyperthermia (PMID: 19648156).  ClinVar contains an entry for this variant (Variation ID: 12969). Experimental studies have shown that this missense change results in altered RYR1 channel properties (PMID: 12732639, 9334205, 9873004). 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: 16917943, 12565913, 23919265). For these reasons, this variant has been classified as Pathogenic.
Leiden Muscular Dystrophy (RYR1) RCV000119406 SCV000154313 not provided not provided no assertion provided not provided
OMIM RCV000013836 SCV000034083 risk factor Malignant hyperthermia, susceptibility to, 1 1998-10-01 no assertion criteria provided literature only
PharmGKB RCV000786476 SCV000925298 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 RCV000786477 SCV000925299 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 RCV000786478 SCV000925300 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 RCV000786479 SCV000925301 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 RCV000786480 SCV000925302 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 RCV000786481 SCV000925303 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 RCV000786482 SCV000925304 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 RCV000119406 SCV000852200 pathogenic not provided 2018-03-15 criteria provided, single submitter clinical testing

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