ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.1453C>G (p.Gln485Glu)

dbSNP: rs1114167803
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 RCV000491767 SCV000580381 uncertain significance Hereditary cancer-predisposing syndrome 2021-12-23 criteria provided, single submitter clinical testing The p.Q485E variant (also known as c.1453C>G), located in coding exon 4 of the MSH6 gene, results from a C to G substitution at nucleotide position 1453. The glutamine at codon 485 is replaced by glutamic acid, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001060245 SCV001224922 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2020-02-27 criteria provided, single submitter clinical testing 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. 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. This variant has not been reported in the literature in individuals with MSH6-related conditions. ClinVar contains an entry for this variant (Variation ID: 428444). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamine with glutamic acid at codon 485 of the MSH6 protein (p.Gln485Glu). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and glutamic acid.
All of Us Research Program, National Institutes of Health RCV004003468 SCV004843633 uncertain significance Lynch syndrome 2023-07-10 criteria provided, single submitter clinical testing This missense variant replaces glutamine with glutamic acid at codon 485 of the MSH6 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MSH6-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is 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.