ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.245C>T (p.Pro82Leu)

gnomAD frequency: 0.00001  dbSNP: rs1190756871
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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 RCV001365780 SCV001562062 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2024-08-20 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 82 of the MSH6 protein (p.Pro82Leu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MSH6-related conditions. ClinVar contains an entry for this variant (Variation ID: 1056885). 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 not expected to disrupt MSH6 protein function with a negative predictive value of 95%. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). 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.
Ambry Genetics RCV002432030 SCV002731636 uncertain significance Hereditary cancer-predisposing syndrome 2024-09-22 criteria provided, single submitter clinical testing The p.P82L variant (also known as c.245C>T), located in coding exon 1 of the MSH6 gene, results from a C to T substitution at nucleotide position 245. The proline at codon 82 is replaced by leucine, an amino acid with similar properties. This amino acid position is well 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.
All of Us Research Program, National Institutes of Health RCV004006792 SCV004842899 uncertain significance Lynch syndrome 2023-11-30 criteria provided, single submitter clinical testing

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