ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1364C>T (p.Ser455Phe) (rs748698776)

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 RCV000167069 SCV000217897 likely benign Hereditary cancer-predisposing syndrome 2017-04-18 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign),Other strong data supporting benign classification
Color RCV000167069 SCV000911128 likely benign Hereditary cancer-predisposing syndrome 2017-05-18 criteria provided, single submitter clinical testing
Invitae RCV000226423 SCV000285067 uncertain significance Hereditary nonpolyposis colon cancer 2018-12-14 criteria provided, single submitter clinical testing This sequence change replaces serine with phenylalanine at codon 455 of the PMS2 protein (p.Ser455Phe). The serine residue is weakly conserved and there is a large physicochemical difference between serine and phenylalanine. This variant is present in population databases (rs748698776, ExAC 0.003%). This variant has been reported in individuals affected with endometrial and colorectal cancer (PMID: 27443514, 23017166). ClinVar contains an entry for this variant (Variation ID: 187347). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: (SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). The phenylalanine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000454673 SCV000540068 uncertain significance not specified 2016-10-13 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Missense variant in PMS2 (Ser to Phe). Max MAF is 0.003% (high for PMS2 related CRC). Classified in ClinVar as VUS by Invitae and Ambry (2 stars). Variant is not reported in the literature. 24 species have Phe at this site.

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.