Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001019404 | SCV001180758 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-09-21 | criteria provided, single submitter | clinical testing | The p.D316E variant (also known as c.948T>G), located in coding exon 10 of the POLE gene, results from a T to G substitution at nucleotide position 948. The aspartic acid at codon 316 is replaced by glutamic acid, 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. |
| Invitae | RCV003541273 | SCV001389829 | uncertain significance | not provided | 2022-05-05 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 316 of the POLE protein (p.Asp316Glu). This variant is present in population databases (rs762898113, gnomAD 0.0009%). 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: 823282). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). 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. |