Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003656478 | SCV001377811 | uncertain significance | not provided | 2021-06-05 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with POLE-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with aspartic acid at codon 1300 of the POLE protein (p.Gly1300Asp). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The aspartic acid amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. |
Ambry Genetics | RCV003373028 | SCV004071001 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-07-04 | criteria provided, single submitter | clinical testing | The p.G1300D variant (also known as c.3899G>A), located in coding exon 31 of the POLE gene, results from a G to A substitution at nucleotide position 3899. The glycine at codon 1300 is replaced by aspartic acid, an amino acid with similar properties. This amino acid position is conserved. 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. |