ClinVar Miner

Submissions for variant NM_000397.4(CYBB):c.626A>G (p.His209Arg)

dbSNP: rs151344482
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000059266 SCV000490940 likely pathogenic not provided 2017-10-24 criteria provided, single submitter clinical testing The H209R variant in the CYBB gene has been published previously in association with chronic granulomatous disease (CGD) (Ishibashi et al., 2000; Kojima et al., 2016). The variant is not observed in large population cohorts (Lek et al., 2016). The variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position within the ferric oxidoreductase domain that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Functional studies on the H209C and H209Y variants have indicated that the H209 residue is critical for heme binding and maturation of flavocytochrome b (Biberstine-Kinkade et al., 2001). Therefore, this variant is likely pathogenic.
Neuberg Centre For Genomic Medicine, NCGM RCV003388571 SCV004100441 likely pathogenic Granulomatous disease, chronic, X-linked criteria provided, single submitter clinical testing The missense variant p.H209R in CYBB (NM_000397.4) gene has been published previously in association with chronic granulomatous disease (CGD) (Ishibashi et al., 2000). Functional studies indicate a damaging effect (Biberstine-Kinkade et al., 2001). The variant has been submitted to ClinVar as Likely Pathogenic.The p.H209R missense variant is predicted to be damaging by both SIFT and PolyPhen2. The histidine residue at codon 209 of CYBB is conserved in all mammalian species. The nucleotide c.626 in CYBB is predicted conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Pathogenic.
UniProtKB/Swiss-Prot RCV000059266 SCV000090795 not provided not provided no assertion provided not provided

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