ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.41T>C (p.Leu14Pro)

dbSNP: rs886043844
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000296459 SCV000342326 uncertain significance not provided 2016-06-06 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003103988 SCV001536163 likely pathogenic Catecholaminergic polymorphic ventricular tachycardia 1 2025-01-31 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 14 of the RYR2 protein (p.Leu14Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with catecholaminergic polymorphic ventricular tachycardia (PMID: 31112425, 35931078). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 288265). 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) indicates that this missense variant is expected to disrupt RYR2 protein function with a positive predictive value of 95%. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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