Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000759972 | SCV000293919 | uncertain significance | not provided | 2023-11-16 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 21157497, 34183866, 20951805) |
Invitae | RCV000474151 | SCV000547597 | uncertain significance | Colorectal cancer, susceptibility to, 10 | 2024-02-01 | 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 312 of the POLD1 protein (p.Val312Met). This variant is present in population databases (rs371612922, gnomAD 0.009%). 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: 246387). 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 | RCV000565647 | SCV000671012 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-09-26 | criteria provided, single submitter | clinical testing | The p.V312M variant (also known as c.934G>A), located in coding exon 7 of the POLD1 gene, results from a G to A substitution at nucleotide position 934. The valine at codon 312 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. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000759972 | SCV000889701 | uncertain significance | not provided | 2017-09-18 | criteria provided, single submitter | clinical testing | |
Institute for Clinical Genetics, |
RCV000759972 | SCV002010598 | uncertain significance | not provided | 2021-11-03 | criteria provided, single submitter | clinical testing | |
Sema4, |
RCV000565647 | SCV002534714 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-03 | criteria provided, single submitter | curation | |
Baylor Genetics | RCV000474151 | SCV004203460 | uncertain significance | Colorectal cancer, susceptibility to, 10 | 2023-09-28 | criteria provided, single submitter | clinical testing | |
Genome |
RCV003483598 | SCV004228733 | not provided | Familial colorectal cancer; Mandibular hypoplasia-deafness-progeroid syndrome | no assertion provided | phenotyping only | Variant interpreted as Uncertain significance and reported on 07-28-2020 by Lab Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. |