ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.1553T>C (p.Val518Ala) (rs1195513704)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000811413 SCV000951679 uncertain significance RYR1-Related Disorders 2018-11-20 criteria provided, single submitter clinical testing This sequence change replaces valine with alanine at codon 518 of the RYR1 protein (p.Val518Ala). The valine residue is highly conserved and there is a small physicochemical difference between valine and alanine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with malignant hyperthermia susceptibility (PMID: 25958340). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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). These observations suggest that a previously unreported missense substitution within this region may affect protein function, but experiments have not been done to test this possibility. 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.
PreventionGenetics RCV000721417 SCV000852479 uncertain significance not provided 2013-11-19 criteria provided, single submitter clinical testing

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