ClinVar Miner

Submissions for variant NM_000397.4(CYBB):c.665A>G (p.His222Arg)

dbSNP: rs151344462
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001854239 SCV002179373 pathogenic Granulomatous disease, chronic, X-linked 2024-02-14 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 222 of the CYBB protein (p.His222Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with chronic granulomatous disease (PMID: 9585602, 10089913, 18546332, 24999735, 29560547). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 68403). 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 with a positive predictive value of 80%. This variant disrupts the p.His222 amino acid residue in CYBB. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9585602, 18546332, 29560547). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
UniProtKB/Swiss-Prot RCV000059270 SCV000090799 not provided not provided no assertion provided not provided

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