ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.1598G>A (p.Arg533His) (rs144336148)

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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 RCV000148808 SCV000190547 uncertain significance Malignant hyperthermia, susceptibility to, 1 2014-06-01 no assertion criteria provided research
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000119578 SCV000203448 uncertain significance not provided 2016-06-06 criteria provided, single submitter clinical testing
Invitae RCV000543445 SCV000659869 uncertain significance RYR1-Related Disorders 2018-12-12 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 533 of the RYR1 protein (p.Arg533His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs144336148, ExAC 0.07%). This variant has been reported in the heterozygous state in an individual affected with malignant hyperthermia (MH) (PMID: 10484775). It has also been reported in the homozygous state in an individual affected with MH, however that individual was homozygous for another variant in the RYR1 gene as well (PMID: 16732084). ClinVar contains an entry for this variant (Variation ID: 133103). Experimental studies have shown that this missense change affects calcium channel function in vitro (PMID: 23459219). This variant disrupts the p.Arg533 amino acid residue in RYR1. Other variant(s) that disrupt this residue have been observed in individuals with RYR1-related conditions (PMID: 12709367), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Leiden Muscular Dystrophy (RYR1) RCV000119578 SCV000154485 not provided not provided no assertion provided not provided
PharmGKB RCV000786487 SCV000925309 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 RCV000786488 SCV000925310 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 RCV000786489 SCV000925311 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 RCV000786490 SCV000925312 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 RCV000786581 SCV000925403 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 RCV000786582 SCV000925404 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 RCV000786583 SCV000925405 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 RCV000119578 SCV000852483 likely pathogenic not provided 2016-02-05 criteria provided, single submitter clinical testing

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