ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.224G>A (p.Gly75Glu)

dbSNP: rs1572698482
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 RCV001014925 SCV001175698 uncertain significance Hereditary cancer-predisposing syndrome 2024-01-17 criteria provided, single submitter clinical testing The p.G75E variant (also known as c.224G>A), located in coding exon 1 of the MSH6 gene, results from a G to A substitution at nucleotide position 224. The glycine at codon 75 is replaced by glutamic acid, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated 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 RCV001216635 SCV001388440 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2021-08-03 criteria provided, single submitter clinical testing This sequence change replaces glycine with glutamic acid at codon 75 of the MSH6 protein (p.Gly75Glu). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and glutamic acid. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant has not been reported in the literature in individuals with MSH6-related conditions. 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 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.
Baylor Genetics RCV003461345 SCV004197739 uncertain significance Endometrial carcinoma 2023-09-13 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.