ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.3947C>T (p.Pro1316Leu)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV004761470 SCV005370902 uncertain significance not provided 2023-07-19 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV005104925 SCV005773038 uncertain significance RYR1-related disorder 2025-01-20 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1316 of the RYR1 protein (p.Pro1316Leu). 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. 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) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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.

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