ClinVar Miner

Submissions for variant NM_002691.4(POLD1):c.1867C>T (p.Arg623Trp)

gnomAD frequency: 0.00001  dbSNP: rs768773535
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
Invitae RCV000553539 SCV000646516 uncertain significance Colorectal cancer, susceptibility to, 10 2023-12-15 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 623 of the POLD1 protein (p.Arg623Trp). This variant is present in population databases (rs768773535, gnomAD 0.006%). 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: 469225). 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.
Fulgent Genetics, Fulgent Genetics RCV000764224 SCV000895227 uncertain significance Colorectal cancer, susceptibility to, 10; Mandibular hypoplasia-deafness-progeroid syndrome 2018-10-31 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001284042 SCV001469616 uncertain significance not provided 2019-12-27 criteria provided, single submitter clinical testing
GeneDx RCV001284042 SCV001796212 uncertain significance not provided 2019-06-05 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 26173643, 29056344)
Ambry Genetics RCV003159854 SCV003912681 uncertain significance Hereditary cancer-predisposing syndrome 2022-12-17 criteria provided, single submitter clinical testing The p.R623W variant (also known as c.1867C>T), located in coding exon 14 of the POLD1 gene, results from a C to T substitution at nucleotide position 1867. The arginine at codon 623 is replaced by tryptophan, an amino acid with dissimilar 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.