Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000698610 | SCV000827285 | uncertain significance | Progressive sclerosing poliodystrophy | 2021-02-16 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with POLG-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with phenylalanine at codon 1106 of the POLG protein (p.Val1106Phe). The valine residue is highly conserved and there is a small physicochemical difference between valine and phenylalanine. 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. 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. |