ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.8330A>G (p.Tyr2777Cys)

dbSNP: rs769276412
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001910645 SCV002196390 uncertain significance RYR1-related disorder 2024-04-10 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 2777 of the RYR1 protein (p.Tyr2777Cys). This variant is present in population databases (rs769276412, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with RYR1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1419820). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt RYR1 protein function with a positive predictive value of 95%. 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.
Revvity Omics, Revvity RCV003130607 SCV003813082 uncertain significance not provided 2019-07-10 criteria provided, single submitter clinical testing
GeneDx RCV003130607 SCV005378152 uncertain significance not provided 2023-10-30 criteria provided, single submitter clinical testing Reported as a secondary finding in a child with epilepsy, but detailed clinical information and familial segregation information were not provided (PMID: 34689486); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 12668474, 34689486)

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