Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001317337 | SCV001507995 | uncertain significance | Neonatal-onset encephalopathy with rigidity and seizures | 2023-11-27 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 192 of the BRAT1 protein (p.Pro192Leu). This variant is present in population databases (rs772270013, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with BRAT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1018087). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt BRAT1 protein function with a positive predictive value of 80%. 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. |
Gene |
RCV001664822 | SCV001873753 | uncertain significance | not provided | 2021-08-10 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 25631046) |
Ambry Genetics | RCV003246872 | SCV003942823 | uncertain significance | Inborn genetic diseases | 2023-06-01 | criteria provided, single submitter | clinical testing | The c.575C>T (p.P192L) alteration is located in exon 5 (coding exon 4) of the BRAT1 gene. This alteration results from a C to T substitution at nucleotide position 575, causing the proline (P) at amino acid position 192 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |