ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.1315C>G (p.Pro439Ala) (rs786203116)

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 RCV000487340 SCV000571801 uncertain significance not provided 2016-09-26 criteria provided, single submitter clinical testing This variant is denoted MSH2 c.1315C>G at the cDNA level, p.Pro439Ala (P439A) at the protein level, and results in the change of a Proline to an Alanine (CCT>GCT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. MSH2 Pro439Ala 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 Alanine differ in some properties, this is considered a semi-conservative amino acid substitution. MSH2 Pro439Ala occurs at a position that is conserved across species and is located in the lever domain, the region of interaction with MSH6, MSH3 and in a region that stabilizes interaction with EXO1 (Lützen 2008). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available evidence, it is unclear whether MSH2 Pro439Ala is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV001010926 SCV001171191 uncertain significance Hereditary cancer-predisposing syndrome 2019-08-16 criteria provided, single submitter clinical testing Insufficient evidence
Cancer Genomics Group,Japanese Foundation For Cancer Research RCV001030709 SCV001193631 uncertain significance Hereditary breast and ovarian cancer syndrome 2019-05-01 criteria provided, single submitter research

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.