ClinVar Miner

Submissions for variant NM_002691.4(POLD1):c.2066G>A (p.Arg689Gln)

gnomAD frequency: 0.00001  dbSNP: rs146530638
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000473890 SCV000547574 uncertain significance Colorectal cancer, susceptibility to, 10 2024-01-27 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 689 of the POLD1 protein (p.Arg689Gln). This variant is present in population databases (rs146530638, gnomAD 0.008%). 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: 408026). 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.
GeneDx RCV000482767 SCV000571173 uncertain significance not provided 2022-12-29 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in individuals with colorectal cancer (Buchanan et al., 2017); This variant is associated with the following publications: (PMID: 32041611, 29120461)
GenomeConnect, ClinGen RCV003227753 SCV003925457 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 05-20-2022 by Invitae. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

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