ClinVar Miner

Submissions for variant NM_002691.4(POLD1):c.952G>A (p.Glu318Lys)

dbSNP: rs775232133
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000538810 SCV000646718 uncertain significance Colorectal cancer, susceptibility to, 10 2023-10-28 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 318 of the POLD1 protein (p.Glu318Lys). This variant is present in population databases (rs775232133, gnomAD 0.0009%). This missense change has been observed in individual(s) with brain tumor and/or endometrial cancer (PMID: 32634176). ClinVar contains an entry for this variant (Variation ID: 469396). 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 expected to disrupt POLD1 protein function with a positive 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 RCV002377118 SCV002688277 uncertain significance Hereditary cancer-predisposing syndrome 2023-01-23 criteria provided, single submitter clinical testing The p.E318K variant (also known as c.952G>A), located in coding exon 7 of the POLD1 gene, results from a G to A substitution at nucleotide position 952. The glutamic acid at codon 318 is replaced by lysine, an amino acid with similar properties. This alteration was identified in an individual diagnosed with uterine cancer (Singh AK et al. PLoS One, 2020 Jul;15:e0235613). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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