Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001017221 | SCV001178264 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-07-12 | criteria provided, single submitter | clinical testing | The p.A361V variant (also known as c.1082C>T), located in coding exon 8 of the POLD1 gene, results from a C to T substitution at nucleotide position 1082. The alanine at codon 361 is replaced by valine, an amino acid with similar properties. This amino acid position is highly 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. |
| Invitae | RCV001037581 | SCV001201004 | uncertain significance | Colorectal cancer, susceptibility to, 10 | 2023-12-27 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 361 of the POLD1 protein (p.Ala361Val). This variant is not present in population databases (gnomAD no frequency). 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: 822127). 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 with a positive 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 |
RCV001766838 | SCV001991131 | uncertain significance | not provided | 2019-05-29 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016); 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 |
| Baylor Genetics | RCV001037581 | SCV004203469 | uncertain significance | Colorectal cancer, susceptibility to, 10 | 2023-09-09 | criteria provided, single submitter | clinical testing |