NM_000397.4(CYBB):c.1014C>G (p.His338Gln) AND Granulomatous disease, chronic, X-linked

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 8, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003059678.3

Allele description [Variation Report for NM_000397.4(CYBB):c.1014C>G (p.His338Gln)]

NM_000397.4(CYBB):c.1014C>G (p.His338Gln)

Gene:

CYBB:cytochrome b-245 beta chain [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xp11.4

Genomic location:

Preferred name:

NM_000397.4(CYBB):c.1014C>G (p.His338Gln)

HGVS:

NC_000023.11:g.37803993C>G
NG_009065.1:g.28977C>G
NM_000397.4:c.1014C>GMANE SELECT
NP_000388.2:p.His338Gln
NP_000388.2:p.His338Gln
LRG_53t1:c.1014C>G
LRG_53:g.28977C>G
LRG_53p1:p.His338Gln
NC_000023.10:g.37663246C>G
NM_000397.3:c.1014C>G

Protein change:

H338Q

Molecular consequence:

NM_000397.4:c.1014C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Granulomatous disease, chronic, X-linked
Synonyms:: CYTOCHROME b-NEGATIVE GRANULOMATOUS DISEASE, CHRONIC, X-LINKED; GRANULOMATOUS DISEASE, CHRONIC, X-LINKED, SOMATIC MOSAIC
Identifiers:: MONDO: MONDO:0010600; MedGen: C1844376; Orphanet: 379; OMIM: 306400

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003354245	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 8, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 20729109, 28251166, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003354245

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 8, 2022)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Hematologically important mutations: X-linked chronic granulomatous disease (third update).

Roos D, Kuhns DB, Maddalena A, Roesler J, Lopez JA, Ariga T, Avcin T, de Boer M, Bustamante J, Condino-Neto A, Di Matteo G, He J, Hill HR, Holland SM, Kannengiesser C, Köker MY, Kondratenko I, van Leeuwen K, Malech HL, Marodi L, Nunoi H, Stasia MJ, et al.

Blood Cells Mol Dis. 2010 Oct 15;45(3):246-65. doi: 10.1016/j.bcmd.2010.07.012. Epub 2010 Aug 21. Review.

PubMed [citation]

PMID:: 20729109
PMCID:: PMC4360070

Clinical Features and Genetic Analysis of 48 Patients with Chronic Granulomatous Disease in a Single Center Study from Shanghai, China (2005-2015): New Studies and a Literature Review.

Wu J, Wang WF, Zhang YD, Chen TX.

J Immunol Res. 2017;2017:8745254. doi: 10.1155/2017/8745254. Epub 2017 Jan 30. Review.

PubMed [citation]

PMID:: 28251166
PMCID:: PMC5303869

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003354245.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This missense change has been observed in individuals with chronic granulomatous disease (PMID: 20729109, 28251166). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with glutamine, which is neutral and polar, at codon 338 of the CYBB protein (p.His338Gln). 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. This variant disrupts the p.His338 amino acid residue in CYBB. Other variant(s) that disrupt this residue have been determined to be pathogenic (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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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