Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001219106 | SCV001391027 | uncertain significance | Neonatal-onset encephalopathy with rigidity and seizures | 2019-06-03 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with alanine at codon 764 of the BRAT1 protein (p.Pro764Ala). The proline residue is weakly conserved and there is a small physicochemical difference between proline and alanine. This variant is present in population databases (rs754574676, ExAC 0.006%). This variant has not been reported in the literature in individuals with BRAT1-related disease. 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, 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. |