Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000759256 | SCV000544068 | uncertain significance | not provided | 2024-12-12 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 34 of the POLE protein (p.Arg34Leu). This variant is present in population databases (no rsID available, gnomAD 0.005%). This missense change has been observed in individual(s) with a family history of breast cancer (PMID: 35534704). ClinVar contains an entry for this variant (Variation ID: 405747). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on POLE protein function. 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. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000759256 | SCV000888484 | uncertain significance | not provided | 2018-05-22 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000759256 | SCV001983013 | uncertain significance | not provided | 2023-10-19 | criteria provided, single submitter | clinical testing | 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; This variant is associated with the following publications: (PMID: 34875656) |
| Ambry Genetics | RCV003168753 | SCV003894383 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-02-27 | criteria provided, single submitter | clinical testing | The p.R34L variant (also known as c.101G>T), located in coding exon 2 of the POLE gene, results from a G to T substitution at nucleotide position 101. The arginine at codon 34 is replaced by leucine, an amino acid with dissimilar 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. |
| Center for Genomic Medicine, |
RCV004596185 | SCV005090000 | uncertain significance | not specified | 2025-03-04 | criteria provided, single submitter | clinical testing |