Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002305488 | SCV000543907 | uncertain significance | not provided | 2023-12-22 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1859 of the POLE protein (p.Leu1859Val). This variant is present in population databases (rs184253572, gnomAD 0.002%). This missense change has been observed in individual(s) with breast cancer (PMID: 35264596). ClinVar contains an entry for this variant (Variation ID: 405601). 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 POLE 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. |
| Mendelics | RCV000709246 | SCV000838677 | uncertain significance | Familial colorectal cancer | 2018-07-02 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV002305488 | SCV002599683 | uncertain significance | not provided | 2022-11-03 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Ambry Genetics | RCV003168742 | SCV003897829 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-11-16 | criteria provided, single submitter | clinical testing | The p.L1859V variant (also known as c.5575C>G), located in coding exon 41 of the POLE gene, results from a C to G substitution at nucleotide position 5575. The leucine at codon 1859 is replaced by valine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |