ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.5183C>T (p.Ser1728Phe) (rs193922781)

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Total submissions: 5
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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 RCV000148807 SCV000265707 pathogenic Malignant hyperthermia, susceptibility to, 1 2013-07-01 criteria provided, single submitter research
PreventionGenetics,PreventionGenetics RCV000119633 SCV000852674 likely pathogenic not provided 2018-07-08 criteria provided, single submitter clinical testing
Invitae RCV001057054 SCV001221528 likely pathogenic RYR1-Related Disorders 2019-12-09 criteria provided, single submitter clinical testing This sequence change replaces serine with phenylalanine at codon 1728 of the RYR1 protein (p.Ser1728Phe). The serine residue is moderately conserved and there is a large physicochemical difference between serine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals and families affected with malignant hyperthermia susceptibility (PMID: 16917943, 19648156, 30236257). ClinVar contains an entry for this variant (Variation ID: 133144). 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 variant disrupts the p.Ser1728 amino acid residue in RYR1. Other variant(s) that disrupt this residue have been observed in individuals with RYR1-related conditions (PMID: 15731587), which suggests that this may be a clinically significant amino acid residue. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Leiden Muscular Dystrophy (RYR1) RCV000119633 SCV000154540 not provided not provided no assertion provided not provided
CSER _CC_NCGL, University of Washington RCV000148807 SCV000190546 pathogenic Malignant hyperthermia, susceptibility to, 1 2014-06-01 no assertion criteria provided research

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