ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.1654A>G (p.Thr552Ala)

dbSNP: rs63750838
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
Invitae RCV000472080 SCV000548152 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2021-08-28 criteria provided, single submitter clinical testing This sequence change replaces threonine with alanine at codon 552 of the MSH2 protein (p.Thr552Ala). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and alanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with MSH2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The alanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Ambry Genetics RCV002402257 SCV002707075 uncertain significance Hereditary cancer-predisposing syndrome 2021-02-03 criteria provided, single submitter clinical testing The p.T552A variant (also known as c.1654A>G), located in coding exon 10 of the MSH2 gene, results from an A to G substitution at nucleotide position 1654. The threonine at codon 552 is replaced by alanine, an amino acid with similar properties. This amino acid position is well 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.
All of Us Research Program, National Institutes of Health RCV004000778 SCV004842959 uncertain significance Lynch syndrome 2023-11-30 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.