ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1075T>G (p.Leu359Val)

dbSNP: rs730881910
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 RCV000160887 SCV000211579 uncertain significance not provided 2015-04-03 criteria provided, single submitter clinical testing This variant is denoted PMS2 c.1075T>G at the cDNA level, p.Leu359Val (L359V) at the protein level, and results in the change of a Leucine to a Valine (TTG>GTG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. PMS2 Leu359Val was not observed in approximately 6,500 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 Leucine and Valine share similar properties, this is considered a conservative amino acid substitution. PMS2 Leu359Val occurs at a position that is highly conserved across species 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 Leu359Val is pathogenic or benign. We consider it to be a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV000477265 SCV000551966 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2025-01-23 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 359 of the PMS2 protein (p.Leu359Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PMS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 182802). Invitae Evidence Modeling incorporating data from in vitro experimental studies (internal data) indicates that this missense variant is not expected to disrupt PMS2 function with a negative predictive value of 95%. 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 RCV001009854 SCV001169974 uncertain significance Hereditary cancer-predisposing syndrome 2019-09-14 criteria provided, single submitter clinical testing The p.L359V variant (also known as c.1075T>G), located in coding exon 10 of the PMS2 gene, results from a T to G substitution at nucleotide position 1075. The leucine at codon 359 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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.