Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000235321 | SCV000289386 | uncertain significance | not provided | 2025-01-12 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 150 of the POLE protein (p.Arg150Gln). This variant is present in population databases (rs780775837, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with POLE-related conditions. ClinVar contains an entry for this variant (Variation ID: 240522). 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) 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. |
| Gene |
RCV000235321 | SCV000293722 | uncertain significance | not provided | 2020-09-17 | 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 |
| Ambry Genetics | RCV000562490 | SCV000674328 | uncertain significance | Hereditary cancer-predisposing syndrome | 2015-06-19 | criteria provided, single submitter | clinical testing | <span style="font-size:12px">Thep.R150Qvariant (also known as c.449G>A), located in codingexon6 of thePOLEgene, results from a G to A substitution at nucleotide position 449. Thearginineatcodon150 is replaced by glutamine, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single NucleotidePolymorphisms(dbSNP),NHLBIExomeSequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. 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 p.R150Q remains unclear. |