ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.124G>A (p.Gly42Ser)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Revvity Omics, Revvity RCV003142717 SCV003820572 uncertain significance not provided 2022-03-01 criteria provided, single submitter clinical testing
GeneDx RCV003142717 SCV005437530 uncertain significance not provided 2024-06-12 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 33767344)
Labcorp Genetics (formerly Invitae), Labcorp RCV005099338 SCV005811023 uncertain significance RYR1-related disorder 2024-12-05 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 42 of the RYR1 protein (p.Gly42Ser). This variant is present in population databases (rs759417601, 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: 2435630). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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.

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