ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.5507C>T (p.Ala1836Val)

gnomAD frequency: 0.00001  dbSNP: rs780776704
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000507374 SCV000289425 uncertain significance not provided 2024-12-29 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1836 of the POLE protein (p.Ala1836Val). This variant is present in population databases (rs780776704, gnomAD 0.002%). 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: 240561). 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000507374 SCV000602069 uncertain significance not provided 2019-06-11 criteria provided, single submitter clinical testing
Ambry Genetics RCV002347895 SCV002650242 uncertain significance Hereditary cancer-predisposing syndrome 2024-12-06 criteria provided, single submitter clinical testing The p.A1836V variant (also known as c.5507C>T), located in coding exon 40 of the POLE gene, results from a C to T substitution at nucleotide position 5507. The alanine at codon 1836 is replaced by valine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.
GeneDx RCV000507374 SCV004021510 uncertain significance not provided 2023-01-23 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: 29641532)

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.