ClinVar Miner

Submissions for variant NM_002691.4(POLD1):c.2340C>G (p.Asp780Glu)

gnomAD frequency: 0.00001  dbSNP: rs572055425
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000470834 SCV000547668 uncertain significance Colorectal cancer, susceptibility to, 10 2024-01-03 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 780 of the POLD1 protein (p.Asp780Glu). This variant is present in population databases (rs572055425, 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: 408115). 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.
Ambry Genetics RCV002446810 SCV002733029 uncertain significance Hereditary cancer-predisposing syndrome 2022-05-17 criteria provided, single submitter clinical testing The p.D780E variant (also known as c.2340C>G), located in coding exon 18 of the POLD1 gene, results from a C to G substitution at nucleotide position 2340. The aspartic acid at codon 780 is replaced by glutamic acid, an amino acid with highly similar 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.

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