Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003656243 | SCV001209300 | uncertain significance | not provided | 2021-09-29 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with POLE-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with isoleucine at codon 1204 of the POLE protein (p.Ser1204Ile). The serine residue is weakly conserved and there is a large physicochemical difference between serine and isoleucine. 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 tolerated. |