ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1399G>C (p.Val467Leu)

dbSNP: rs373611083
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000775703 SCV000910117 uncertain significance Hereditary cancer-predisposing syndrome 2019-01-19 criteria provided, single submitter clinical testing
Invitae RCV001873156 SCV002112862 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2021-11-02 criteria provided, single submitter clinical testing 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. 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 PMS2 protein function. ClinVar contains an entry for this variant (Variation ID: 630430). This variant has not been reported in the literature in individuals affected with PMS2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 467 of the PMS2 protein (p.Val467Leu).
Ambry Genetics RCV000775703 SCV004005609 uncertain significance Hereditary cancer-predisposing syndrome 2023-05-24 criteria provided, single submitter clinical testing The p.V467L variant (also known as c.1399G>C), located in coding exon 11 of the PMS2 gene, results from a G to C substitution at nucleotide position 1399. The valine at codon 467 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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