ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.100A>C (p.Ser34Arg) (rs730881912)

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
GeneDx RCV000160889 SCV000211581 uncertain significance not provided 2015-05-29 criteria provided, single submitter clinical testing This variant is denoted PMS2 c.100A>C at the cDNA level, p.Ser34Arg (S34R) at the protein level, and results in the change of a Serine to an Arginine (AGT>CGT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. PMS2 Ser34Arg was not observed in approximately 3,700 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating 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 Ser34Arg occurs at a position that is conserved in mammals and is located in the ATPase domain (Fukui 2011). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available information, it is unclear whether PMS2 Ser34Arg is pathogenic or benign. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000216392 SCV000274297 uncertain significance Hereditary cancer-predisposing syndrome 2019-03-12 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Invitae RCV000548098 SCV000625493 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-11-04 criteria provided, single submitter clinical testing This sequence change replaces serine with arginine at codon 34 of the PMS2 protein (p.Ser34Arg). 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 disease. ClinVar contains an entry for this variant (Variation ID: 182804). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.

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.