ClinVar Miner

Submissions for variant NM_002691.4(POLD1):c.3170A>G (p.Gln1057Arg)

dbSNP: rs768747132
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000532197 SCV000646637 uncertain significance Colorectal cancer, susceptibility to, 10 2023-12-30 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 1057 of the POLD1 protein (p.Gln1057Arg). This variant is present in population databases (rs768747132, gnomAD 0.0009%). 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: 469327). 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 RCV001764579 SCV002000829 uncertain significance not provided 2020-02-25 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); 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
Ambry Genetics RCV002324002 SCV002610017 uncertain significance Hereditary cancer-predisposing syndrome 2024-06-23 criteria provided, single submitter clinical testing The p.Q1057R variant (also known as c.3170A>G), located in coding exon 25 of the POLD1 gene, results from an A to G substitution at nucleotide position 3170. The glutamine at codon 1057 is replaced by arginine, an amino acid with highly 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.
Fulgent Genetics, Fulgent Genetics RCV005027648 SCV005650326 uncertain significance Colorectal cancer, susceptibility to, 10; Mandibular hypoplasia-deafness-progeroid syndrome; Immunodeficiency 120 2024-05-20 criteria provided, single submitter clinical testing

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