Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000816608 | SCV000957125 | uncertain significance | Colorectal cancer, susceptibility to, 10 | 2023-12-22 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with tyrosine, which is neutral and polar, at codon 1042 of the POLD1 protein (p.Ser1042Tyr). This variant is present in population databases (rs370868833, 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: 659577). 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 | RCV003166356 | SCV003912880 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-12-04 | criteria provided, single submitter | clinical testing | The p.S1042Y variant (also known as c.3125C>A), located in coding exon 25 of the POLD1 gene, results from a C to A substitution at nucleotide position 3125. The serine at codon 1042 is replaced by tyrosine, an amino acid with dissimilar 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. |