ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.1589G>A (p.Arg530His) (rs111888148)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CSER_CC_NCGL; University of Washington Medical Center RCV000148805 SCV000190543 pathogenic Malignant hyperthermia, susceptibility to, 1 2014-06-01 no assertion criteria provided research
Illumina Clinical Services Laboratory,Illumina RCV000148805 SCV000914844 uncertain significance Malignant hyperthermia, susceptibility to, 1 2018-10-26 criteria provided, single submitter clinical testing The RYR1 c.1589G>A (p.Arg530His) variant is a missense variant that has been reported in two studies, in which it is found in a heterozygous state in a total of four individuals with malignant hyperthermia susceptibility, including three affected individuals from one family (Zullo et al. 2009; Levano et al. 2009). The p.Arg530His variant was shown to segregate with disease in the family (Zullo et al. 2009). The p.Arg530His variant was absent from 200 controls and is reported at a frequency of 0.000259 in the Latino population of the Exome Aggregation Consortium. Epstein-Barr virus immortalized B lymphocytes from an affected individual showed significantly higher extracellular acidification for the p.Arg530His variant compared to wild type (Zullo et al. 2009). Based on the evidence, the p.Arg530His variant is classified as a variant of unknown significance but suspicious for pathogenicity for malignant hyperthermia susceptibility. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV000655554 SCV000777485 pathogenic RYR1-Related Disorders 2018-12-28 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 530 of the RYR1 protein (p.Arg530His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs111888148, ExAC 0.03%). This variant has been reported in several individuals and families with RYR1-related disease (PMID: 19191333, 16917943, 19191329, 26578207). This variant has been reported to segregate with malignant hyperthermia susceptibility in a family (PMID: 19191333). ClinVar contains an entry for this variant (Variation ID: 133101). Experimental studies have shown that this missense change alters RYR1 channel function (PMID: 19191333, 27646467). 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.
Leiden Muscular Dystrophy (RYR1) RCV000119576 SCV000154483 not provided not provided no assertion provided not provided
PharmGKB RCV000786418 SCV000925240 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 RCV000786541 SCV000925363 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 RCV000786542 SCV000925364 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 RCV000786543 SCV000925365 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 RCV000786544 SCV000925366 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 RCV000786545 SCV000925367 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 RCV000786546 SCV000925368 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 RCV000119576 SCV000852482 likely pathogenic not provided 2015-12-14 criteria provided, single submitter clinical testing

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