ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.11958C>G (p.Asp3986Glu) (rs193922842)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000210014 SCV000265745 pathogenic Malignant hyperthermia, susceptibility to, 1 2013-07-01 criteria provided, single submitter research
Invitae RCV000531152 SCV000659782 pathogenic RYR1-Related Disorders 2017-07-24 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with glutamic acid at codon 3986 of the RYR1 protein (p.Asp3986Glu). The aspartic acid residue is moderately conserved and there is a small physicochemical difference between aspartic acid and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several individuals affected with malignant hyperthermia (PMID: 16917943, 19648156,24195946, 23558838, 25658027). ClinVar contains an entry for this variant (Variation ID: 133026). Experimental studies have shown that this missense change causes an increased sensitivity to contracture inducing caffeine and halothane (PMID: 19648156, 23558838).  Serum creatine kinase levels were also found to be significantly higher in samples from individuals carrying this variant (PMID: 19648156). For these reasons, this variant has been classified as Pathogenic.
PreventionGenetics,PreventionGenetics RCV000119446 SCV000852276 likely pathogenic not provided 2013-11-22 criteria provided, single submitter clinical testing
Leiden Muscular Dystrophy (RYR1) RCV000119446 SCV000154353 not provided not provided no assertion provided not provided

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