ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.2564A>G (p.Gln855Arg) (rs587782256)

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 RCV000130969 SCV000185884 uncertain significance Hereditary cancer-predisposing syndrome 2017-08-01 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
GeneDx RCV000483907 SCV000570435 uncertain significance not provided 2016-05-24 criteria provided, single submitter clinical testing This variant is denoted MSH2 c.2564A>G at the cDNA level, p.Gln855Arg (Q855R) at the protein level, and results in the change of a Glutamine to an Arginine (CAG>CGG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. MSH2 Gln855Arg was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Glutamine and Arginine differ in some properties, this is considered a semi-conservative amino acid substitution. MSH2 Gln855Arg occurs at a position that is conserved across species and is located in the ATPase domain (Lützen 2008). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether MSH2 Gln855Arg is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000547275 SCV000625390 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-09-12 criteria provided, single submitter clinical testing This sequence change replaces glutamine with arginine at codon 855 of the MSH2 protein (p.Gln855Arg). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MSH2-related disease. ClinVar contains an entry for this variant (Variation ID: 142129). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.