ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.2107A>G (p.Met703Val)

gnomAD frequency: 0.00001  dbSNP: rs751867550
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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000227011 SCV000283742 likely benign Hereditary nonpolyposis colorectal neoplasms 2024-01-17 criteria provided, single submitter clinical testing
GeneDx RCV000483631 SCV000565222 uncertain significance not provided 2023-05-09 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; Observed in at least one individual referred for hereditary cancer testing (Paulo et al., 2017); This variant is associated with the following publications: (PMID: 17531815, 21120944, 28529006)
Color Diagnostics, LLC DBA Color Health RCV000580465 SCV000685257 uncertain significance Hereditary cancer-predisposing syndrome 2023-07-06 criteria provided, single submitter clinical testing This missense variant replaces methionine with valine at codon 703 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 not been reported in individuals affected with MSH6-related disorders in the literature. This variant has been identified in 4/276460 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.
Counsyl RCV000662419 SCV000784855 uncertain significance Lynch syndrome 5 2017-01-11 criteria provided, single submitter clinical testing
Mendelics RCV000662419 SCV001135815 uncertain significance Lynch syndrome 5 2019-05-28 criteria provided, single submitter clinical testing
Ambry Genetics RCV000580465 SCV001175163 uncertain significance Hereditary cancer-predisposing syndrome 2022-08-09 criteria provided, single submitter clinical testing The p.M703V variant (also known as c.2107A>G), located in coding exon 4 of the MSH6 gene, results from an A to G substitution at nucleotide position 2107. The methionine at codon 703 is replaced by valine, an amino acid with highly 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.
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV000483631 SCV002010109 uncertain significance not provided 2021-11-03 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV000662419 SCV004018449 uncertain significance Lynch syndrome 5 2023-03-27 criteria provided, single submitter clinical testing This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.
Baylor Genetics RCV003469132 SCV004195569 uncertain significance Endometrial carcinoma 2023-08-21 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV003998715 SCV004843857 uncertain significance Lynch syndrome 2023-12-07 criteria provided, single submitter clinical testing This missense variant replaces methionine with valine at codon 703 of the MSH6 protein. Computational prediction tool 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 performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 4/276460 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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