ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.12443A>C (p.Asn4148Thr)

dbSNP: rs1213878810
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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 RCV000721272 SCV000852296 uncertain significance not provided 2016-08-18 criteria provided, single submitter clinical testing
GeneDx RCV000721272 SCV001982078 uncertain significance not provided 2021-09-17 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); 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
Labcorp Genetics (formerly Invitae), Labcorp RCV001868377 SCV002284927 uncertain significance RYR1-related disorder 2022-08-09 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with threonine, which is neutral and polar, at codon 4148 of the RYR1 protein (p.Asn4148Thr). This variant is not present in population databases (gnomAD no frequency). 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: 590403). 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. 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 RCV000721272 SCV003812399 uncertain significance not provided 2020-03-18 criteria provided, single submitter clinical testing
Genetics and Molecular Pathology, SA Pathology RCV003447557 SCV004175465 uncertain significance Central core myopathy 2021-12-20 criteria provided, single submitter clinical testing

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