ClinVar Miner

Submissions for variant NM_002691.4(POLD1):c.3001G>A (p.Gly1001Ser)

gnomAD frequency: 0.00001  dbSNP: rs550922227
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001035083 SCV001198397 uncertain significance Colorectal cancer, susceptibility to, 10 2024-01-21 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1001 of the POLD1 protein (p.Gly1001Ser). 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: 834404). 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.
GeneDx RCV001732017 SCV001982066 uncertain significance not provided 2023-09-07 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 28481359, 19296856)
Baylor Genetics RCV001788402 SCV002030137 uncertain significance Mandibular hypoplasia-deafness-progeroid syndrome 2021-07-22 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Ambry Genetics RCV002434425 SCV002748655 uncertain significance Hereditary cancer-predisposing syndrome 2021-11-12 criteria provided, single submitter clinical testing The p.G1001S variant (also known as c.3001G>A), located in coding exon 23 of the POLD1 gene, results from a G to A substitution at nucleotide position 3001. The glycine at codon 1001 is replaced by serine, an amino acid with similar 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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