Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000530654 | SCV000646643 | uncertain significance | Colorectal cancer, susceptibility to, 10 | 2023-03-22 | criteria provided, single submitter | clinical testing | 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. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). 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. ClinVar contains an entry for this variant (Variation ID: 469332). This variant has not been reported in the literature in individuals affected with POLD1-related conditions. This variant is present in population databases (rs774127655, gnomAD 0.0009%). This sequence change replaces methionine, which is neutral and non-polar, with lysine, which is basic and polar, at codon 1081 of the POLD1 protein (p.Met1081Lys). |
Ambry Genetics | RCV003159859 | SCV003912591 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-01-01 | criteria provided, single submitter | clinical testing | The p.M1081K variant (also known as c.3242T>A), located in coding exon 26 of the POLD1 gene, results from a T to A substitution at nucleotide position 3242. The methionine at codon 1081 is replaced by lysine, an amino acid with 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. |