ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.2099C>T (p.Pro700Leu)

gnomAD frequency: 0.00002  dbSNP: rs777002868
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001563170 SCV000544055 uncertain significance not provided 2025-02-02 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 700 of the POLE protein (p.Pro700Leu). This variant is present in population databases (rs777002868, gnomAD 0.006%). 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: 405735). 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.
Mendelics RCV000709269 SCV000838700 likely benign Familial colorectal cancer 2024-04-01 criteria provided, single submitter clinical testing
GeneDx RCV001563170 SCV001786061 uncertain significance not provided 2022-12-23 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); 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; This variant is associated with the following publications: (PMID: 31034466, 20951805)
Sema4, Sema4 RCV002258903 SCV002536776 uncertain significance Hereditary cancer-predisposing syndrome 2021-05-18 criteria provided, single submitter curation
Ambry Genetics RCV002258903 SCV002724510 uncertain significance Hereditary cancer-predisposing syndrome 2022-10-03 criteria provided, single submitter clinical testing The p.P700L variant (also known as c.2099C>T), located in coding exon 19 of the POLE gene, results from a C to T substitution at nucleotide position 2099. The proline at codon 700 is replaced by leucine, an amino acid with similar properties. This amino acid position is conserved. 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.