ClinVar Miner

Submissions for variant NM_002691.4(POLD1):c.3197A>G (p.His1066Arg)

gnomAD frequency: 0.00001  dbSNP: rs762828545
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000542366 SCV000646638 uncertain significance Colorectal cancer, susceptibility to, 10 2023-07-14 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 1066 of the POLD1 protein (p.His1066Arg). This variant is present in population databases (rs762828545, gnomAD 0.003%). 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: 469328). 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. 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.
Ambry Genetics RCV002324003 SCV002610797 uncertain significance Hereditary cancer-predisposing syndrome 2024-01-12 criteria provided, single submitter clinical testing The p.H1066R variant (also known as c.3197A>G), located in coding exon 25 of the POLD1 gene, results from an A to G substitution at nucleotide position 3197. The histidine at codon 1066 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 RCV005027649 SCV005650327 uncertain significance Colorectal cancer, susceptibility to, 10; Mandibular hypoplasia-deafness-progeroid syndrome; Immunodeficiency 120 2023-12-29 criteria provided, single submitter clinical testing

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