ClinVar Miner

Submissions for variant NM_000397.4(CYBB):c.1244C>T (p.Pro415Leu)

dbSNP: rs137854585
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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 RCV002513777 SCV003444553 pathogenic Granulomatous disease, chronic, X-linked 2022-08-16 criteria provided, single submitter clinical testing Experimental studies have shown that this missense change affects CYBB function (PMID: 20724480). This variant disrupts the p.Pro415 amino acid residue in CYBB. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 2556453, 11162142, 20724480; Invitae). 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. 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. ClinVar contains an entry for this variant (Variation ID: 68378). This variant is also known as NOX2 gene, c.1256C>T. This missense change has been observed in individuals with chronic granulomatous disease (CGD) (PMID: 9585602, 22562447). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 415 of the CYBB protein (p.Pro415Leu).
UniProtKB/Swiss-Prot RCV000059238 SCV000090767 not provided not provided no assertion provided not provided

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