ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.6584C>T (p.Pro2195Leu)

gnomAD frequency: 0.00001  dbSNP: rs772003357
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PreventionGenetics, part of Exact Sciences RCV000721617 SCV000852718 uncertain significance not provided 2018-09-10 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000800253 SCV000939954 pathogenic RYR1-related disorder 2023-01-22 criteria provided, single submitter clinical testing This missense change has been observed in individual(s) with clinical features of autosomal dominant congenital myopathy (PMID: 25214167; Invitae). In at least one individual the variant was observed to be de novo. 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. ClinVar contains an entry for this variant (Variation ID: 590572). This variant is present in population databases (rs772003357, gnomAD 0.005%). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 2195 of the RYR1 protein (p.Pro2195Leu).
GeneDx RCV000721617 SCV002102649 pathogenic not provided 2024-09-18 criteria provided, single submitter clinical testing Reported as heterozygous in an individual with congenital myopathy, but familial segregation information was not provided (PMID: 25214167); 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; This variant is associated with the following publications: (PMID: 12668474, 25214167, 32236737)
Institute of Human Genetics, Clinical Exome/Genome Diagnostics Group, University Hospital Bonn RCV000721617 SCV002496422 uncertain significance not provided 2022-03-24 criteria provided, single submitter clinical testing PP3, PP5
Revvity Omics, Revvity RCV000721617 SCV003813092 uncertain significance not provided 2019-12-01 criteria provided, single submitter clinical testing

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