Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000469418 | SCV000547496 | uncertain significance | Colorectal cancer, susceptibility to, 10 | 2023-12-13 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 455 of the POLD1 protein (p.Val455Met). This variant is present in population databases (rs762670703, gnomAD 0.003%). 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: 407953). 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. |
Gene |
RCV000487202 | SCV000569634 | uncertain significance | not provided | 2022-09-16 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 20951805) |
Ambry Genetics | RCV000570540 | SCV000671030 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-02 | criteria provided, single submitter | clinical testing | The p.V455M variant (also known as c.1363G>A), located in coding exon 10 of the POLD1 gene, results from a G to A substitution at nucleotide position 1363. The valine at codon 455 is replaced by methionine, an amino acid with highly 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. |
Fulgent Genetics, |
RCV000764221 | SCV000895224 | uncertain significance | Colorectal cancer, susceptibility to, 10; Mandibular hypoplasia-deafness-progeroid syndrome | 2018-10-31 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV000469418 | SCV004203438 | uncertain significance | Colorectal cancer, susceptibility to, 10 | 2023-10-26 | criteria provided, single submitter | clinical testing |