ClinVar Miner

Submissions for variant NM_002691.4(POLD1):c.520C>T (p.Arg174Trp)

gnomAD frequency: 0.00003  dbSNP: rs749334182
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 RCV000231174 SCV000287633 uncertain significance Colorectal cancer, susceptibility to, 10 2025-01-30 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 174 of the POLD1 protein (p.Arg174Trp). This variant is present in population databases (rs749334182, gnomAD 0.02%). This missense change has been observed in individual(s) with attenuated adenomatous polyposis (PMID: 31285513). ClinVar contains an entry for this variant (Variation ID: 239351). 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 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.
GeneDx RCV001568780 SCV001792708 uncertain significance not provided 2022-06-29 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in individuals with attenuated polyposis (Lorca 2019); This variant is associated with the following publications: (PMID: 31285513)
Ambry Genetics RCV004943800 SCV005470093 likely benign Hereditary cancer-predisposing syndrome 2024-08-23 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Molecular Oncology Laboratory, Hospital Clínico San Carlos RCV000231174 SCV000844935 uncertain significance Colorectal cancer, susceptibility to, 10 2018-06-01 no assertion criteria provided 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.