Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000485581 | SCV000570046 | uncertain significance | not provided | 2019-12-23 | criteria provided, single submitter | clinical testing | While protein-based in silico analysis supports that this variant does not alter protein structure/function, splice predictors suggest this variant may impact gene splicing. In the absence of RNA or functional studies, the actual effect of this sequence change is unknown.; Has not been previously published as a pathogenic or benign germline variant to our knowledge; This variant is associated with the following publications: (PMID: 29056344) |
| Invitae | RCV000533107 | SCV000646517 | uncertain significance | Colorectal cancer, susceptibility to, 10 | 2023-08-24 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 623 of the POLD1 protein (p.Arg623Gln). This variant is present in population databases (rs781327088, gnomAD 0.01%). 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: 420987). 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 | RCV003168954 | SCV003909026 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-11-17 | criteria provided, single submitter | clinical testing | The p.R623Q variant (also known as c.1868G>A), located in coding exon 14 of the POLD1 gene, results from a G to A substitution at nucleotide position 1868. The arginine at codon 623 is replaced by glutamine, 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. |