ClinVar Miner

Submissions for variant NM_002691.4(POLD1):c.2458G>A (p.Ala820Thr)

gnomAD frequency: 0.00001  dbSNP: rs753609023
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000549076 SCV000646564 uncertain significance Colorectal cancer, susceptibility to, 10 2024-01-19 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 820 of the POLD1 protein (p.Ala820Thr). This variant is present in population databases (rs753609023, gnomAD 0.01%). 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: 469265). 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.
GeneDx RCV003153713 SCV003842575 uncertain significance not provided 2023-02-22 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 20951805, 31034466)
GenomeConnect - Invitae Patient Insights Network RCV001535544 SCV001749519 not provided Colorectal cancer, susceptibility to, 10; Mandibular hypoplasia-deafness-progeroid syndrome no assertion provided phenotyping only Variant interpreted as Uncertain significance and reported on 06-26-2019 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.

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