Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003541305 | SCV001404057 | uncertain significance | not provided | 2022-09-24 | criteria provided, single submitter | clinical testing | 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. 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 POLE protein function. ClinVar contains an entry for this variant (Variation ID: 958376). This variant has not been reported in the literature in individuals affected with POLE-related conditions. This variant is present in population databases (rs781702191, gnomAD 0.003%). This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 962 of the POLE protein (p.Asp962Gly). |
Ambry Genetics | RCV002436902 | SCV002750494 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-12 | criteria provided, single submitter | clinical testing | The p.D962G variant (also known as c.2885A>G), located in coding exon 25 of the POLE gene, results from an A to G substitution at nucleotide position 2885. The aspartic acid at codon 962 is replaced by glycine, an amino acid with 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. |