ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.2626G>T (p.Glu876Ter)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000798885 SCV000938524 pathogenic Hereditary nonpolyposis colon cancer 2018-11-01 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the MSH2 gene (p.Glu876*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 59 amino acids of the MSH2 protein. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333). This variant is expected to disrupt nearly the entire C-terminal portion of the MSH6 and MSH3 interaction domains of the MSH2 protein, as well as the helix-turn-helix domain (PMID: 9774676, 18822302, 17531815). Although functional studies have not been done for this particular variant, loss of the C-terminal region of the protein likely impairs MSH2 function (PMID: 9774676, 18822302, 17531815). Other variant(s) that disrupt this region (p.Gln879*, p.Ile883Leufs*9, p.Leu888Cysfs*4) have been determined to be pathogenic (PMID: 15858146, 11579115, 14970868, 9222765, 8640829). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.

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.