Submissions for variant NM_000397.3(CYBB):c.1223G>A (p.Gly408Glu) (rs151344474)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000059236	SCV000322410	pathogenic	not provided	2016-02-26	criteria provided, single submitter	clinical testing	The G408E missense variant in the CYBB gene has been reported previously in association with X-linked Chronic Granulomatous Disease (CGD) (O'Neill et al., 2015; Rae et al., 1998). The G408E variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This non-conservative amino acid substitution occurs at a position in the NADPH-binding domain that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. Functional studies confirm that the G408 residue is essential for NADPH oxidase complex activity, and that the G408E variant specifically disturbs the normal electron transfer from NADPH to FAD leading to a defective NAD incorporation in the binding site. (Debeurme et al., 2010). Missense variants in the same (G408R) and nearby residues (M405R, G412R/E) have been reported in the Human Gene Mutation Database in association with X-linked CGD (Stenson et al., 2014).
UniProtKB/Swiss-Prot	RCV000059236	SCV000090765	not provided	not provided		no assertion provided	not provided