ClinVar Miner

Submissions for variant NM_002691.4(POLD1):c.3022C>T (p.Arg1008Cys)

gnomAD frequency: 0.00001  dbSNP: rs1044937882
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000473681 SCV000547491 uncertain significance Colorectal cancer, susceptibility to, 10 2023-10-13 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1008 of the POLD1 protein (p.Arg1008Cys). 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: 407948). 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 RCV002436417 SCV002753089 uncertain significance Hereditary cancer-predisposing syndrome 2021-06-23 criteria provided, single submitter clinical testing The p.R1008C variant (also known as c.3022C>T), located in coding exon 23 of the POLD1 gene, results from a C to T substitution at nucleotide position 3022. The arginine at codon 1008 is replaced by cysteine, an amino acid with highly dissimilar 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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