ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.2132G>A (p.Arg711Gln) (rs138465383)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000563683 SCV000673913 uncertain significance Hereditary cancer-predisposing syndrome 2019-10-08 criteria provided, single submitter clinical testing Insufficient evidence;In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
University of Washington Department of Laboratory Medicine, University of Washington RCV000758589 SCV000887338 uncertain significance Lynch syndrome 2018-05-01 criteria provided, single submitter clinical testing MSH2 NM_000251.2:c.2132G>A has a 63.2% probability of pathogenicity based on combining prior probability from public data with a likelihood ratio of 0.20 to 1, generated from evidence of seeing this as a somatic mutation in a tumor without loss of heterozygosity at the MSH2 locus. See Shirts et al 2018, PMID 29887214.
Invitae RCV000792263 SCV000931545 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2018-11-18 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 711 of the MSH2 protein (p.Arg711Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs138465383, ExAC 0.006%). This variant has been reported in individuals in the Universal Mutation Database (PMID: 10612827). ClinVar contains an entry for this variant (Variation ID: 485849). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but 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.
Color RCV000563683 SCV001352950 uncertain significance Hereditary cancer-predisposing syndrome 2019-09-12 criteria provided, single submitter clinical testing

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.