ClinVar Miner

Submissions for variant NM_000397.4(CYBB):c.1609T>C (p.Cys537Arg)

dbSNP: rs151344454
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000059248 SCV000521157 pathogenic not provided 2023-09-19 criteria provided, single submitter clinical testing Published functional studies demonstrate the variant nearly abolishes NADPH oxidase activity and leads to steric conflicts likely incompatible with NADPH orientation (Debeurme et al., 2010); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 21190454, 12139950, 12589359, 26210446, 9585602, 20729109, 29560547, 34175765, 31172472, 35796921, 28168067, 22540226, 30506560, 20724480)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000585928 SCV000696682 pathogenic Granulomatous disease, chronic, X-linked 2017-03-30 criteria provided, single submitter clinical testing Variant summary: The CYBB c.1609T>C (p.Cys537Arg) variant located in the NADPH binding domain involves the alteration of a conserved nucleotide and 5/5 in silico tools predict a damaging outcome. Multiple functional studies, Jirapongsananuruk_2003, de Oliveria-Junior_2012, and Desbeurme_2010 indicate that the variant has a pathogenic effect on the protein, imparticular causing no detectable NADPH oxidase activity. The variant of interest was not observed in 86762 control chromosomes (ExAC) and multiple publications have cited the variant in affected individuals. Furthermore, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV000585928 SCV000950724 pathogenic Granulomatous disease, chronic, X-linked 2018-12-04 criteria provided, single submitter clinical testing This variant has been observed in several individuals affected with X-linked chronic granulomatous disease (PMID: 22540226, 28168067, 12589359, 9585602). This variant is also referred to as c.1621T>C in the literature. ClinVar contains an entry for this variant (Variation ID: 68386). This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with arginine at codon 537 of the CYBB protein (p.Cys537Arg). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and arginine. This variant has been reported to affect CYBB protein function (PMID: 20724480). For these reasons, this variant has been classified as Pathogenic.
UniProtKB/Swiss-Prot RCV000059248 SCV000090777 not provided not provided no assertion provided not provided

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.