ClinVar Miner

Submissions for variant NM_002691.4(POLD1):c.820G>A (p.Ala274Thr)

gnomAD frequency: 0.00001  dbSNP: rs878854557
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000229086 SCV000287652 uncertain significance Colorectal cancer, susceptibility to, 10 2023-08-31 criteria provided, single submitter clinical testing 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. 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. ClinVar contains an entry for this variant (Variation ID: 239370). This variant has not been reported in the literature in individuals affected with POLD1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.005%). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 274 of the POLD1 protein (p.Ala274Thr).
GeneDx RCV002298546 SCV002588217 uncertain significance not provided 2022-10-27 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 25344691, 29056344)
Fulgent Genetics, Fulgent Genetics RCV002487066 SCV002780591 uncertain significance Colorectal cancer, susceptibility to, 10; Mandibular hypoplasia-deafness-progeroid syndrome 2022-02-02 criteria provided, single submitter 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.