NM_004004.6(GJB2):c.353_356dup (p.Glu119fs) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 29, 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:: RCV003727128.2

Allele description [Variation Report for NM_004004.6(GJB2):c.353_356dup (p.Glu119fs)]

NM_004004.6(GJB2):c.353_356dup (p.Glu119fs)

Gene:

GJB2:gap junction protein beta 2 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

13q12.11

Genomic location:

Preferred name:

NM_004004.6(GJB2):c.353_356dup (p.Glu119fs)

HGVS:

NC_000013.11:g.20189227_20189230dup
NG_008358.1:g.8747_8750dup
NM_004004.6:c.353_356dupMANE SELECT
NP_003995.2:p.Glu119fs
LRG_1350t1:c.353_356dup
LRG_1350:g.8747_8750dup
LRG_1350p1:p.Glu119fs
NC_000013.10:g.20763364_20763365insTCGA
NC_000013.10:g.20763366_20763369dup

Protein change:

E119fs

Molecular consequence:

NM_004004.6:c.353_356dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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sulfhydryl oxidase 2 precursor [Homo sapiens]
sulfhydryl oxidase 2 precursor [Homo sapiens]
gi|145580631|ref|NP_859052.3|

Protein
LOC108466051 [Gossypium arboreum]
LOC108466051 [Gossypium arboreum]
Gene ID:108466051

Gene
Receptors, G-Protein-Coupled
Receptors, G-Protein-Coupled
The largest family of cell surface receptors involved in SIGNAL TRANSDUCTION. They share a common structure and signal through HETEROTRIMERIC G-PROTEINS....<br/>Year introduced: 2004

MeSH

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004535451	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 29, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 23141775, 29196752, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004535451

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 29, 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

A novel p.Leu213X mutation in GJB2 gene in a Portuguese family.

Gonçalves AC, Chora J, Matos TD, Santos R, O'Neill A, Escada P, Fialho G, Caria H.

Int J Pediatr Otorhinolaryngol. 2013 Jan;77(1):89-91. doi: 10.1016/j.ijporl.2012.10.002. Epub 2012 Nov 8.

PubMed [citation]

PMID:: 23141775

Combined genetic approaches yield a 48% diagnostic rate in a large cohort of French hearing-impaired patients.

Baux D, Vaché C, Blanchet C, Willems M, Baudoin C, Moclyn M, Faugère V, Touraine R, Isidor B, Dupin-Deguine D, Nizon M, Vincent M, Mercier S, Calais C, García-García G, Azher Z, Lambert L, Perdomo-Trujillo Y, Giuliano F, Claustres M, Koenig M, Mondain M, et al.

Sci Rep. 2017 Dec 1;7(1):16783. doi: 10.1038/s41598-017-16846-9.

PubMed [citation]

PMID:: 29196752
PMCID:: PMC5711943

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004535451.1

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the GJB2 protein in which other variant(s) (p.Leu213*) have been determined to be pathogenic (PMID: 23141775). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This premature translational stop signal has been observed in individual(s) with autosomal recessive GJB2-related conditions (PMID: 29196752). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu119Aspfs*92) in the GJB2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 108 amino acid(s) of the GJB2 protein.

#	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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