ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1450C>T (p.Pro484Ser)

dbSNP: rs752122569
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000483475 SCV000570609 uncertain significance not provided 2016-06-10 criteria provided, single submitter clinical testing This variant is denoted PMS2 c.1450C>T at the cDNA level, p.Pro484Ser (P484S) at the protein level, and results in the change of a Proline to a Serine (CCT>TCT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. PMS2 Pro484Ser was not observed in approximately 6,500 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 Proline and Serine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. PMS2 Pro484Ser occurs at a position that is not conserved and is not located in a known functional domain (Guarne 2001, Fukui 2011). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available evidence, it is unclear whether PMS2 Pro484Ser is pathogenic or benign. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV002395164 SCV002696863 uncertain significance Hereditary cancer-predisposing syndrome 2020-01-16 criteria provided, single submitter clinical testing The p.P484S variant (also known as c.1450C>T), located in coding exon 11 of the PMS2 gene, results from a C to T substitution at nucleotide position 1450. The proline at codon 484 is replaced by serine, an amino acid with similar properties. This amino acid position is poorly 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.

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.