ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.2569A>G (p.Ile857Val) (rs753459308)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000574140 SCV000662321 uncertain significance Hereditary cancer-predisposing syndrome 2016-11-17 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
PreventionGenetics,PreventionGenetics RCV000679307 SCV000806033 uncertain significance not provided 2017-10-27 criteria provided, single submitter clinical testing
Invitae RCV000694840 SCV000823302 uncertain significance Hereditary nonpolyposis colon cancer 2018-01-11 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with valine at codon 857 of the MSH2 protein (p.Ile857Val). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and valine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with MSH2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have 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.

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.