ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.698C>T (p.Pro233Leu)

dbSNP: rs142949377
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001206362 SCV001377668 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2023-02-27 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 233 of the MSH6 protein (p.Pro233Leu). 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: 937367). 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 MSH6 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.
Ambry Genetics RCV002365931 SCV002664442 uncertain significance Hereditary cancer-predisposing syndrome 2024-11-07 criteria provided, single submitter clinical testing The p.P233L variant (also known as c.698C>T), located in coding exon 4 of the MSH6 gene, results from a C to T substitution at nucleotide position 698. The proline at codon 233 is replaced by leucine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.
All of Us Research Program, National Institutes of Health RCV004010645 SCV004834442 uncertain significance Lynch syndrome 2024-01-11 criteria provided, single submitter clinical testing
Baylor Genetics RCV004570439 SCV005054868 uncertain significance Endometrial carcinoma 2024-03-07 criteria provided, single submitter clinical testing

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