ClinVar Miner

Submissions for variant NM_002691.4(POLD1):c.2158G>A (p.Val720Ile)

dbSNP: rs1042614681
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001218023 SCV001389890 uncertain significance Colorectal cancer, susceptibility to, 10 2023-11-15 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 720 of the POLD1 protein (p.Val720Ile). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with POLD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 947038). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt POLD1 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.
Ambry Genetics RCV002429926 SCV002731269 uncertain significance Hereditary cancer-predisposing syndrome 2022-03-23 criteria provided, single submitter clinical testing The p.V720I variant (also known as c.2158G>A), located in coding exon 17 of the POLD1 gene, results from a G to A substitution at nucleotide position 2158. The valine at codon 720 is replaced by isoleucine, an amino acid with highly 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.