Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003509047 | SCV004298953 | uncertain significance | Granulomatous disease, chronic, X-linked | 2023-08-07 | criteria provided, single submitter | clinical testing | This missense change has been observed in individuals with clinical features of chronic granulomatous disease (PMID: 20729109; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 179 of the CYBB protein (p.Gly179Glu). 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 CYBB protein function. This variant disrupts the p.Gly179 amino acid residue in CYBB. Other variant(s) that disrupt this residue have been observed in individuals with CYBB-related conditions (PMID: 9794433), which suggests that this may be a clinically significant amino acid residue. 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. |