ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.2614A>G (p.Ile872Val)

dbSNP: rs1060502939
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000470821 SCV000551281 likely benign Hereditary nonpolyposis colorectal neoplasms 2023-11-21 criteria provided, single submitter clinical testing
Ambry Genetics RCV000491946 SCV000580373 uncertain significance Hereditary cancer-predisposing syndrome 2024-02-01 criteria provided, single submitter clinical testing The p.I872V variant (also known as c.2614A>G), located in coding exon 4 of the MSH6 gene, results from an A to G substitution at nucleotide position 2614. The isoleucine at codon 872 is replaced by valine, an amino acid with highly 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 alteration remains unclear.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759137 SCV000888263 uncertain significance not provided 2017-10-03 criteria provided, single submitter clinical testing
GeneDx RCV000759137 SCV002576892 uncertain significance not provided 2022-03-30 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: 23621914, 17531815, 21120944)
All of Us Research Program, National Institutes of Health RCV004001855 SCV004832260 uncertain significance Lynch syndrome 2023-08-23 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with valine at codon 872 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 1/250062 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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