ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.2180C>G (p.Thr727Ser)

gnomAD frequency: 0.00001  dbSNP: rs767861096
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000629678 SCV000750634 benign Hereditary nonpolyposis colorectal neoplasms 2023-08-01 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000774601 SCV000908392 uncertain significance Hereditary cancer-predisposing syndrome 2023-06-01 criteria provided, single submitter clinical testing This missense variant replaces threonine with serine at codon 727 of the MSH6 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MSH6-related disorders in the literature. This variant has been identified in 1/250942 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.
Ambry Genetics RCV000774601 SCV001175454 uncertain significance Hereditary cancer-predisposing syndrome 2024-03-13 criteria provided, single submitter clinical testing The p.T727S variant (also known as c.2180C>G), located in coding exon 4 of the MSH6 gene, results from a C to G substitution at nucleotide position 2180. The threonine at codon 727 is replaced by serine, an amino acid with 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.
All of Us Research Program, National Institutes of Health RCV004002769 SCV004836129 uncertain significance Lynch syndrome 2023-12-13 criteria provided, single submitter clinical testing This missense variant replaces threonine with serine at codon 727 of the MSH6 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MSH6-related disorders in the literature. This variant has been identified in 1/250942 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.
GeneDx RCV004767454 SCV005378188 uncertain significance not provided 2023-11-03 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 17531815, 21120944)

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