ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.1028C>T (p.Pro343Leu)

gnomAD frequency: 0.00001  dbSNP: rs548898238
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000212641 SCV000149275 uncertain significance not provided 2023-11-06 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 21437237, 36091175, 25318351)
Ambry Genetics RCV000115366 SCV000186100 uncertain significance Hereditary cancer-predisposing syndrome 2024-05-27 criteria provided, single submitter clinical testing The p.P343L variant (also known as c.1028C>T), located in coding exon 4 of the MSH6 gene, results from a C to T substitution at nucleotide position 1028. The proline at codon 343 is replaced by leucine, an amino acid with some similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV000469621 SCV000551201 benign Hereditary nonpolyposis colorectal neoplasms 2024-12-10 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000212641 SCV002046242 uncertain significance not provided 2020-09-25 criteria provided, single submitter clinical testing
Baylor Genetics RCV004566998 SCV005055021 uncertain significance Endometrial carcinoma 2023-11-29 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004806063 SCV005429249 uncertain significance Lynch syndrome 2024-03-24 criteria provided, single submitter clinical testing This missense variant replaces proline with leucine at codon 343 of the MSH6 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual who underwent genetic hereditary cancer testing (PMID: 25318351). This variant has also been reported in an individual affected with malignant seminoma (PMID: 36091175). This variant has been identified in 2/282698 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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