ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.5914G>A (p.Val1972Met)

gnomAD frequency: 0.00001  dbSNP: rs774726229
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
Labcorp Genetics (formerly Invitae), Labcorp RCV001569038 SCV000824760 uncertain significance not provided 2024-11-27 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 1972 of the POLE protein (p.Val1972Met). This variant is present in population databases (rs774726229, 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: 574304). 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.
GeneDx RCV001569038 SCV001793019 uncertain significance not provided 2021-03-31 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 29056344, 27244218)
PreventionGenetics, part of Exact Sciences RCV004535733 SCV004733075 uncertain significance POLE-related disorder 2024-01-24 no assertion criteria provided clinical testing The POLE c.5914G>A variant is predicted to result in the amino acid substitution p.Val1972Met. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0054% of alleles in individuals of East Asian descent in gnomAD and is interpreted as a variant of uncertain significance in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/574304/). 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.