ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.6599C>T (p.Ala2200Val) (rs193922791)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000688108 SCV000815708 uncertain significance RYR1-Related Disorders 2018-08-29 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 2200 of the RYR1 protein (p.Ala2200Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs193922791, ExAC 0.01%). This variant has been reported in several individuals affected with malignant hyperthermia susceptibility (PMID: 15731587, 16835904, 21455645). ClinVar contains an entry for this variant (Variation ID: 133162). 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"). 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: 16917943, 12565913, 23919265). These observations suggest that missense substitutions 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.
Leiden Muscular Dystrophy (RYR1) RCV000119659 SCV000154566 not provided not provided no assertion provided not provided
PreventionGenetics RCV000119659 SCV000852719 likely pathogenic not provided 2013-11-20 criteria provided, single submitter clinical testing

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