Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000807734 | SCV000947803 | uncertain significance | Neonatal-onset encephalopathy with rigidity and seizures | 2018-12-13 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with BRAT1-related disease. 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant is not present in population databases (ExAC no frequency). This sequence change replaces phenylalanine with leucine at codon 83 of the BRAT1 protein (p.Phe83Leu). The phenylalanine residue is moderately conserved and there is a small physicochemical difference between phenylalanine and leucine. |
Gene |
RCV001772087 | SCV001992530 | uncertain significance | not provided | 2019-04-30 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts; In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |