ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.1450G>C (p.Glu484Gln) (rs587782706)

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 RCV000132161 SCV000187236 uncertain significance Hereditary cancer-predisposing syndrome 2017-05-09 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Invitae RCV000203804 SCV000260923 uncertain significance Hereditary nonpolyposis colon cancer 2018-08-21 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with glutamine at codon 484 of the MSH6 protein (p.Glu484Gln). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with an MSH6-related disease. ClinVar contains an entry for this variant (Variation ID: 142768). 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.
GeneDx RCV000480825 SCV000565994 uncertain significance not provided 2018-05-17 criteria provided, single submitter clinical testing This variant is denoted MSH6 c.1450G>C at the cDNA level, p.Glu484Gln (E484Q) at the protein level, and results in the change of a Glutamic Acid to a Glutamine (GAA>CAA). This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. MSH6 Glu484Gln was not observed in large population cohorts (Lek 2016). This variant is located in the mismatch binding domain (Warren 2007, Kansikas 2011). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether MSH6 Glu484Gln is a pathogenic or benign variant. We consider it to be 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.