ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.2083C>G (p.Leu695Val)

dbSNP: rs1669418611
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001192034 SCV001359978 uncertain significance Hereditary cancer-predisposing syndrome 2023-04-22 criteria provided, single submitter clinical testing This missense variant replaces leucine with valine at codon 695 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 not been identified 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 RCV001192034 SCV002727795 uncertain significance Hereditary cancer-predisposing syndrome 2021-11-05 criteria provided, single submitter clinical testing The p.L695V variant (also known as c.2083C>G), located in coding exon 4 of the MSH6 gene, results from a C to G substitution at nucleotide position 2083. The leucine at codon 695 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.
Baylor Genetics RCV003462666 SCV004197648 uncertain significance Endometrial carcinoma 2023-10-10 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004010566 SCV004843824 uncertain significance Lynch syndrome 2023-05-04 criteria provided, single submitter clinical testing This missense variant replaces leucine with valine at codon 695 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). Splice site prediction tools suggest that this variant may not impact RNA splicing. 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 not been identified 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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