Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000601615 | SCV000712645 | uncertain significance | not specified | 2016-11-23 | criteria provided, single submitter | clinical testing | The p.Glu579Lys variant in POLD1 has not been previously reported in individuals with colorectal cancer or in large population studies. Computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Glu579Lys variant is uncertain. |
| Invitae | RCV000799439 | SCV000939101 | uncertain significance | Colorectal cancer, susceptibility to, 10 | 2023-11-29 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 579 of the POLD1 protein (p.Glu579Lys). This variant is present in population databases (no rsID available, gnomAD 0.007%). 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: 505438). 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. |
| Ambry Genetics | RCV002404616 | SCV002710200 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-10-30 | criteria provided, single submitter | clinical testing | The p.E579K variant (also known as c.1735G>A), located in coding exon 13 of the POLD1 gene, results from a G to A substitution at nucleotide position 1735. The glutamic acid at codon 579 is replaced by lysine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |