ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.8107C>A (p.Pro2703Thr)

gnomAD frequency: 0.00001  dbSNP: rs763186606
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002553141 SCV001210244 uncertain significance Catecholaminergic polymorphic ventricular tachycardia 1 2024-10-16 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 2703 of the RYR2 protein (p.Pro2703Thr). This variant is present in population databases (rs763186606, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with RYR2-related conditions. ClinVar contains an entry for this variant (Variation ID: 843671). 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 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.
AiLife Diagnostics, AiLife Diagnostics RCV002223260 SCV002501125 uncertain significance not provided 2022-01-18 criteria provided, single submitter clinical testing
Ambry Genetics RCV002416369 SCV002679025 uncertain significance Cardiovascular phenotype 2023-03-15 criteria provided, single submitter clinical testing The p.P2703T variant (also known as c.8107C>A), located in coding exon 53 of the RYR2 gene, results from a C to A substitution at nucleotide position 8107. The proline at codon 2703 is replaced by threonine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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