Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003656382 | SCV001228979 | uncertain significance | not provided | 2019-02-27 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with serine at codon 1149 of the POLE protein (p.Ala1149Ser). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and serine. 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with POLE-related conditions. |
| Ambry Genetics | RCV002451276 | SCV002617144 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-09-21 | criteria provided, single submitter | clinical testing | The p.A1149S variant (also known as c.3445G>T), located in coding exon 28 of the POLE gene, results from a G to T substitution at nucleotide position 3445. The alanine at codon 1149 is replaced by serine, 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. |