ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.14378T>C (p.Leu4793Pro)

dbSNP: rs118192179
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PreventionGenetics, part of Exact Sciences RCV000119508 SCV000852404 uncertain significance not provided 2016-06-24 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001854162 SCV002145858 pathogenic RYR1-related disorder 2021-04-02 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. 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. This variant has been observed in individual(s) with autosomal dominant central core disease (PMID: 11709545, Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 65962). This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with proline at codon 4793 of the RYR1 protein (p.Leu4793Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline.
GeneReviews RCV000056209 SCV000087298 pathologic Central core myopathy 2010-05-11 no assertion criteria provided curation Converted during submission to Pathogenic.
Leiden Muscular Dystrophy (RYR1) RCV000119508 SCV000154415 not provided not provided no assertion provided not provided

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