ClinVar Miner

Submissions for variant NM_002691.4(POLD1):c.1294C>G (p.Arg432Gly)

dbSNP: rs774130423
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000462290 SCV000547501 uncertain significance Colorectal cancer, susceptibility to, 10 2023-09-29 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with POLD1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 432 of the POLD1 protein (p.Arg432Gly). ClinVar contains an entry for this variant (Variation ID: 407957). 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. 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.
Fulgent Genetics, Fulgent Genetics RCV000764219 SCV000895222 uncertain significance Colorectal cancer, susceptibility to, 10; Mandibular hypoplasia-deafness-progeroid syndrome 2018-10-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV001010805 SCV001171054 uncertain significance Hereditary cancer-predisposing syndrome 2022-09-12 criteria provided, single submitter clinical testing The p.R432G variant (also known as c.1294C>G), located in coding exon 10 of the POLD1 gene, results from a C to G substitution at nucleotide position 1294. The arginine at codon 432 is replaced by glycine, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. 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.
Sema4, Sema4 RCV001010805 SCV002534576 uncertain significance Hereditary cancer-predisposing syndrome 2021-08-18 criteria provided, single submitter curation
GeneDx RCV003441871 SCV004168064 uncertain significance not provided 2023-10-19 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 20951805)

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