ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.1411A>G (p.Met471Val)

gnomAD frequency: 0.00004  dbSNP: rs749021187
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
Ambry Genetics RCV000575792 SCV000671446 uncertain significance Hereditary cancer-predisposing syndrome 2023-07-25 criteria provided, single submitter clinical testing The p.M471V variant (also known as c.1411A>G), located in coding exon 14 of the POLE gene, results from an A to G substitution at nucleotide position 1411. The methionine at codon 471 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001731793 SCV000834711 uncertain significance not provided 2025-01-23 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 471 of the POLE protein (p.Met471Val). This variant is present in population databases (rs749021187, gnomAD 0.01%). 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: 484462). 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 expected to disrupt POLE protein function with a positive 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.
GeneDx RCV001731793 SCV001982646 uncertain significance not provided 2023-09-08 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: 20951805, 37268062)
Sema4, Sema4 RCV000575792 SCV002536754 uncertain significance Hereditary cancer-predisposing syndrome 2021-07-22 criteria provided, single submitter curation
Baylor Genetics RCV000705700 SCV004203514 uncertain significance Colorectal cancer, susceptibility to, 12 2023-11-18 criteria provided, single submitter clinical testing

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.