ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.2090C>T (p.Pro697Leu)

dbSNP: rs36120395
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000759272 SCV000543966 uncertain significance not provided 2024-11-27 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 697 of the POLE protein (p.Pro697Leu). This variant is present in population databases (rs36120395, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with POLE-related conditions. ClinVar contains an entry for this variant (Variation ID: 405654). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt POLE protein function with a negative predictive value of 80%. 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.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000602076 SCV000731329 uncertain significance not specified 2016-12-28 criteria provided, single submitter clinical testing The p.Pro697Leu variant in POLE has not been previously reported in individuals with colorectal cancer, but has been identified in 1/11552 of Latino chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSN P rs36120395). Computational prediction tools and conservation analysis do not p rovide strong support for or against an impact to the protein. In summary, the c linical significance of the p.Pro697Leu variant is uncertain.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759272 SCV000888507 uncertain significance not provided 2018-06-06 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000763812 SCV000894729 uncertain significance Colorectal cancer, susceptibility to, 12; Facial dysmorphism-immunodeficiency-livedo-short stature syndrome 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000759272 SCV001738315 uncertain significance not provided 2020-02-07 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function Has not been previously published as pathogenic or benign to our knowledge
PreventionGenetics, part of Exact Sciences RCV004737498 SCV005347374 uncertain significance POLE-related disorder 2024-06-08 no assertion criteria provided clinical testing The POLE c.2090C>T variant is predicted to result in the amino acid substitution p.Pro697Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0078% of alleles in individuals of European (Non-Finnish) descent in gnomAD and is interpreted as uncertain significance (https://www.ncbi.nlm.nih.gov/clinvar/variation/405654/?new_evidence=true). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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.