Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002038937 | SCV002309477 | uncertain significance | Progressive sclerosing poliodystrophy | 2020-11-23 | 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. 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with POLG-related conditions. This variant is present in population databases (rs767900699, ExAC 0.01%). This sequence change replaces proline with leucine at codon 483 of the POLG protein (p.Pro483Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. |