ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.2600T>G (p.Val867Gly) (rs139598980)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130173 SCV000185010 likely benign Hereditary cancer-predisposing syndrome 2020-09-01 criteria provided, single submitter clinical testing In silico models in agreement (benign);Other data supporting benign classification
GeneDx RCV000222583 SCV000279104 uncertain significance not provided 2021-03-09 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Observed in individuals with a personal history of rectal cancer (de Rosa 2016); This variant is associated with the following publications: (PMID: 23621914, 27432916)
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphia RCV000238642 SCV000296880 uncertain significance Lynch syndrome 2015-11-19 criteria provided, single submitter clinical testing
Invitae RCV000524147 SCV000551103 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2020-10-14 criteria provided, single submitter clinical testing This sequence change replaces valine with glycine at codon 867 of the MSH6 protein (p.Val867Gly). The valine residue is moderately conserved and there is a moderate physicochemical difference between valine and glycine. This variant is present in population databases (rs139598980, ExAC 0.01%). This variant has been reported in an individual affected with colorectal cancer (PMID: 27432916). ClinVar contains an entry for this variant (Variation ID: 141589). An algorithm developed specifically for the MSH6 gene (PMID: 23621914), suggests that this missense change is likely to be tolerated. However, this prediction has not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Color Health, Inc RCV000130173 SCV000685301 uncertain significance Hereditary cancer-predisposing syndrome 2020-09-30 criteria provided, single submitter clinical testing This missense variant replaces valine with glycine at codon 867 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). 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 been reported in an individual affected with rectal cancer (PMID: 27432916). This variant has been identified in 9/281252 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.