ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.106A>C (p.Ser36Arg) (rs587781918)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130264 SCV000185108 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-03 criteria provided, single submitter clinical testing Insufficient evidence
Invitae RCV000228325 SCV000285042 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-12-23 criteria provided, single submitter clinical testing This sequence change replaces serine with arginine at codon 36 of the PMS2 protein (p.Ser36Arg). The serine residue is weakly conserved and there is a moderate physicochemical difference between serine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with PMS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 141660). This variant has been reported not to substantially affect PMS2 protein function (PMID: 28494185). 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.
GeneDx RCV000484647 SCV000566579 uncertain significance not provided 2017-02-17 criteria provided, single submitter clinical testing This variant is denoted PMS2 c.106A>C at the cDNA level, p.Ser36Arg (S36R) at the protein level, and results in the change of a Serine to an Arginine (AGC>CGC). This variant has not, to our knowledge, been published in the literature as a germline variant; however, it has been reported as a somatic variant in glioma (Suzuki 2015). PMS2 Ser36Arg was not observed in approximately 3,700 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Serine and Arginine differ in some properties, this is considered a semi-conservative amino acid substitution. PMS2 Ser36Arg occurs at a position that is not conserved and is located in the ATPase domain (Guarne 2001). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether PMS2 Ser36Arg is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Counsyl RCV000662593 SCV000785222 uncertain significance Hereditary nonpolyposis colorectal cancer type 4 2017-06-08 criteria provided, single submitter clinical testing
Color RCV000130264 SCV000909682 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-31 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.