ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1928A>G (p.Gln643Arg) (rs760629688)

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
Invitae RCV000463007 SCV000551970 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2020-09-30 criteria provided, single submitter clinical testing This sequence change replaces glutamine with arginine at codon 643 of the PMS2 protein (p.Gln643Arg). The glutamine residue is weakly conserved and there is a small physicochemical difference between glutamine and arginine. This variant is present in population databases (rs760629688, ExAC 0.08%). This variant has been reported in an individual affected with Lynch syndrome (PMID: 24710284). ClinVar contains an entry for this variant (Variation ID: 411037). 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. 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 RCV000573574 SCV000663528 uncertain significance Hereditary cancer-predisposing syndrome 2017-12-08 criteria provided, single submitter clinical testing The p.Q643R variant (also known as c.1928A>G), located in coding exon 11 of the PMS2 gene, results from an A to G substitution at nucleotide position 1928. The glutamine at codon 643 is replaced by arginine, an amino acid with highly similar properties. This alteration, classified as a variant of uncertain significance, was identified in one family from Singapore who met either Amsterdam I or Amsterdam II criteria (Liu Y et al. PLoS ONE, 2014 Apr;9:e94170). This amino acid position is 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.
Fulgent Genetics,Fulgent Genetics RCV000765955 SCV000897376 uncertain significance Turcot syndrome; Hereditary nonpolyposis colorectal cancer type 4 2018-10-31 criteria provided, single submitter clinical testing
Color Health, Inc RCV000573574 SCV000911418 likely benign Hereditary cancer-predisposing syndrome 2016-05-30 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.