ClinVar Miner

Submissions for variant NM_002691.4(POLD1):c.1918A>G (p.Thr640Ala)

gnomAD frequency: 0.00002  dbSNP: rs201212113
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 RCV000645808 SCV000767563 uncertain significance Colorectal cancer, susceptibility to, 10 2024-01-19 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 640 of the POLD1 protein (p.Thr640Ala). This variant is present in population databases (rs201212113, gnomAD 0.03%). 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: 537065). 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759221 SCV000888441 uncertain significance not provided 2020-02-28 criteria provided, single submitter clinical testing
GeneDx RCV000759221 SCV001819802 uncertain significance not provided 2021-05-27 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (Lek 2016); This variant is associated with the following publications: (PMID: 29056344)
Fulgent Genetics, Fulgent Genetics RCV002507106 SCV002815308 uncertain significance Colorectal cancer, susceptibility to, 10; Mandibular hypoplasia-deafness-progeroid syndrome 2021-10-19 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003424225 SCV004118654 uncertain significance POLD1-related condition 2023-01-25 criteria provided, single submitter clinical testing The POLD1 c.1918A>G variant is predicted to result in the amino acid substitution p.Thr640Ala. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.031% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/19-50912404-A-G). In ClinVar, this variant is interpreted as uncertain (https://preview.ncbi.nlm.nih.gov/clinvar/variation/537065/). Although we suspect that this variant may be benign, 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.