ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.11126C>T (p.Ala3709Val) (rs1555791418)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000538941 SCV000659760 uncertain significance RYR1-Related Disorders 2018-10-23 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 3709 of the RYR1 protein (p.Ala3709Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with malignant hyperthermia (PMID: 21965348). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. While it is absent from the population and reported in affected individuals, the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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