ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.13120G>A (p.Val4374Met)

gnomAD frequency: 0.00001  dbSNP: rs1973363499
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001056885 SCV001221350 uncertain significance RYR1-Related Disorders 2022-02-09 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 4374 of the RYR1 protein (p.Val4374Met). 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: 852305). 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 not 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.
PreventionGenetics, part of Exact Sciences RCV003938424 SCV004760942 uncertain significance RYR1-related condition 2024-01-08 criteria provided, single submitter clinical testing The RYR1 c.13120G>A variant is predicted to result in the amino acid substitution p.Val4374Met. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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