ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1192G>C (p.Glu398Gln)

gnomAD frequency: 0.00001  dbSNP: rs1171400724
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000575562 SCV000676167 uncertain significance Hereditary cancer-predisposing syndrome 2020-12-31 criteria provided, single submitter clinical testing The p.E398Q variant (also known as c.1192G>C), located in coding exon 11 of the PMS2 gene, results from a G to C substitution at nucleotide position 1192. The glutamic acid at codon 398 is replaced by glutamine, an amino acid with highly 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.
Invitae RCV000629728 SCV000750684 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2023-07-18 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PMS2 protein function. ClinVar contains an entry for this variant (Variation ID: 486923). This missense change has been observed in individual(s) with juvenile hamartomatous polyps (PMID: 27146957). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 398 of the PMS2 protein (p.Glu398Gln).
Color Diagnostics, LLC DBA Color Health RCV000575562 SCV000913141 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-05 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004001199 SCV004839839 uncertain significance Lynch syndrome 2023-06-15 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.