ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.2786G>A (p.Arg929Gln) (rs587779967)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000759829 SCV000149430 uncertain significance not provided 2015-06-05 criteria provided, single submitter clinical testing This variant is denoted MSH2 c.2786G>A at the cDNA level, p.Arg929Gln (R929Q) at the protein level, and results in the change of an Arginine to a Glutamine (CGA>CAA). It has not been published as a germline pathogenic variant, nor has it been reported as a benign polymorphism, to our knowledge. However, the MSH2 Arg929Gln amino acid substitution has previously been reported as a somatic change in one endometrial tumor according to the Catalogue of Somatic Mutations in Cancer (COSMIC). MSH2 Arg929Gln was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Arginine and Glutamine differ in some properties, this is considered a semi-conservative amino acid substitution. MSH2 Arg929Gln occurs at a position that is not conserved and is located within the region of interaction with MSH6 and MSH3 (Lutzen 2008). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available information, it is unclear whether MSH2 Arg929Gln is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000469769 SCV000548126 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-12-11 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 929 of the MSH2 protein (p.Arg929Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs587779967, ExAC 0.009%) but has not been reported in the literature in individuals with a MSH2-related disease. ClinVar contains an entry for this variant (Variation ID: 127639). 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 tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Color RCV000583830 SCV000690097 uncertain significance Hereditary cancer-predisposing syndrome 2019-12-18 criteria provided, single submitter clinical testing
Counsyl RCV000662933 SCV000785889 uncertain significance Lynch syndrome I 2018-01-04 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759829 SCV000889431 uncertain significance not provided 2019-02-13 criteria provided, single submitter clinical testing
Ambry Genetics RCV000583830 SCV001177570 uncertain significance Hereditary cancer-predisposing syndrome 2019-02-12 criteria provided, single submitter clinical testing Insufficient evidence

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.