Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000550403 | SCV000646716 | uncertain significance | Colorectal cancer, susceptibility to, 10 | 2023-06-21 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 314 of the POLD1 protein (p.Ser314Gly). 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. 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 expected to disrupt POLD1 protein function. ClinVar contains an entry for this variant (Variation ID: 469395). This variant has not been reported in the literature in individuals affected with POLD1-related conditions. This variant is not present in population databases (gnomAD no frequency). |
Ambry Genetics | RCV000572421 | SCV000671165 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-10-25 | criteria provided, single submitter | clinical testing | The p.S314G variant (also known as c.940A>G), located in coding exon 7 of the POLD1 gene, results from an A to G substitution at nucleotide position 940. The serine at codon 314 is replaced by glycine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. 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. |
Gene |
RCV001770458 | SCV001992948 | uncertain significance | not provided | 2019-06-21 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016); Has not been previously published as pathogenic or benign to our knowledge |
Baylor Genetics | RCV000550403 | SCV004203442 | uncertain significance | Colorectal cancer, susceptibility to, 10 | 2023-10-20 | criteria provided, single submitter | clinical testing |