ClinVar Miner

Submissions for variant NM_002691.4(POLD1):c.1289A>G (p.Asn430Ser)

gnomAD frequency: 0.00001  dbSNP: rs546554950
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000561845 SCV000671057 uncertain significance Hereditary cancer-predisposing syndrome 2021-08-06 criteria provided, single submitter clinical testing The p.N430S variant (also known as c.1289A>G), located in coding exon 10 of the POLD1 gene, results from an A to G substitution at nucleotide position 1289. The asparagine at codon 430 is replaced by serine, an amino acid with highly similar properties. This amino acid position is not 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.
Invitae RCV000807683 SCV000947749 uncertain significance Colorectal cancer, susceptibility to, 10 2024-01-29 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 430 of the POLD1 protein (p.Asn430Ser). 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: 484349). 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 with a negative 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.
Mendelics RCV000807683 SCV001141142 uncertain significance Colorectal cancer, susceptibility to, 10 2019-05-28 criteria provided, single submitter clinical testing
Baylor Genetics RCV000807683 SCV004203500 uncertain significance Colorectal cancer, susceptibility to, 10 2023-05-26 criteria provided, single submitter clinical testing

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