NM_004004.6(GJB2):c.355GAG[1] (p.Glu120del) AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (5 submissions)
Last evaluated:: Jan 24, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000520132.34

Allele description

NM_004004.6(GJB2):c.355GAG[1] (p.Glu120del)

Gene:

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

Variant type:

Microsatellite

Cytogenetic location:

13q12.11

Genomic location:

Preferred name:

NM_004004.6(GJB2):c.355GAG[1] (p.Glu120del)

Other names:

E118del; E120delE

HGVS:

NC_000013.10:g.20763361_20763363del
NC_000013.11:g.20189222CTC[1]
NG_008358.1:g.8749GAG[1]
NM_004004.6:c.355GAG[1]MANE SELECT
NM_004004.6:c.358_360delGAG
NP_003995.2:p.Glu120del
LRG_1350t1:c.355GAG[1]
LRG_1350:g.8749GAG[1]
LRG_1350p1:p.Glu120del
NC_000013.10:g.20763361CTC[1]
NC_000013.10:g.20763361_20763363del
NC_000013.10:g.20763361_20763363delCTC
NC_000013.11:g.20189222_20189224delCTC
NM_004004.5:c.358_360delGAG
NM_004004.6:c.355GAG[1]
NM_004004.6:c.358_360delMANE SELECT
NM_004004.6:c.358_360delGAGMANE SELECT
c.358_360delGAG
c.358_360delGAG (p.Glu120del)

Protein change:

E120del; GLU118DEL

Links:

OMIM: 121011.0007; dbSNP: rs80338947

NCBI 1000 Genomes Browser:

rs80338947

Molecular consequence:

NM_004004.6:c.355GAG[1] - inframe_deletion - [Sequence Ontology: SO:0001822]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000617686	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Nov 24, 2021)	germline	clinical testing	Citation Link,
SCV000841706	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Pathogenic (Mar 16, 2018)	germline	clinical testing	PubMed (19) [See all records that cite these PMIDs] 10544226, 11438992, 12505163, 18941476, 20609484, 15617550, 16712961, 12673800, 15967879, 27169813, 20059378, 23668481, 28405014, 27340645, 20234132, 19371219, 22975760, 15070423, 26467025
SCV000945066	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 24, 2024)	germline	clinical testing	PubMed (10) [See all records that cite these PMIDs] 10544226, 11438992, 15070423, 16712961, 20553101, 20609484, 25214170, 12505163, 18941476, 28492532
SCV001747686	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Jul 1, 2021)	germline	clinical testing	Citation Link,
SCV005199406	Clinical Genetics Laboratory, Skane University Hospital Lund	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 27, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	3	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Low prevalence of Connexin 26 (GJB2) variants in Pakistani families with autosomal recessive non-syndromic hearing impairment.

Santos RL, Wajid M, Pham TL, Hussan J, Ali G, Ahmad W, Leal SM.

Clin Genet. 2005 Jan;67(1):61-8.

PubMed [citation]

PMID:: 15617550
PMCID:: PMC2909104

Spectrum of GJB2 mutations in Turkey comprises both Caucasian and Oriental variants: roles of parental consanguinity and assortative mating.

Tekin M, Duman T, Boğoçlu G, Incesulu A, Comak E, Ilhan I, Akar N.

Hum Mutat. 2003 May;21(5):552-3.

PubMed [citation]

PMID:: 12673800

See all PubMed Citations (23)

Details of each submission

From GeneDx, SCV000617686.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

In-frame deletion of one amino acid in the cytoplasmic loop, a non-repeat region; Published functional studies demonstrate c.358_360delGAG impairs the function of gap channels (Bruzzone et al., 2003; Mani et al., 2009); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 22975760, 29485809, 15070423, 11438992, 20609484, 10544226, 12673800, 15666300, 15967879, 16712961, 12505163, 18941476, 27573290, 27177978, 29501291, 31160754, 32747562, 33096615, 31589614, 33105617, 34581455, 34695157)

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

From Athena Diagnostics, SCV000841706.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (19)

#	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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000945066.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (10)

Description

This variant, c.358_360del, results in the deletion of 1 amino acid(s) of the GJB2 protein (p.Glu120del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs80338947, gnomAD 0.01%). This variant has been observed in individuals with autosomal recessive deafness (PMID: 10544226, 11438992, 15070423, 16712961, 18941476, 20553101, 20609484, 25214170). ClinVar contains an entry for this variant (Variation ID: 17006). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this variant affects GJB2 function (PMID: 12505163, 18941476). 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

From CeGaT Center for Human Genetics Tuebingen, SCV001747686.18

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		3	not provided	not provided	not provided

From Clinical Genetics Laboratory, Skane University Hospital Lund, SCV005199406.1

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

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

Last Updated: Sep 29, 2024

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