ClinVar Miner

Submissions for variant NM_002691.4(POLD1):c.1933G>A (p.Glu645Lys)

dbSNP: rs1161281976
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000558260 SCV000646519 uncertain significance Colorectal cancer, susceptibility to, 10 2023-10-18 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 645 of the POLD1 protein (p.Glu645Lys). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 469227). 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. 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 RCV002413571 SCV002721314 uncertain significance Hereditary cancer-predisposing syndrome 2021-12-18 criteria provided, single submitter clinical testing The p.E645K variant (also known as c.1933G>A), located in coding exon 15 of the POLD1 gene, results from a G to A substitution at nucleotide position 1933. The glutamic acid at codon 645 is replaced by lysine, an amino acid with 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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