NM_004004.6(GJB2):c.379C>T (p.Arg127Cys) AND Rare genetic deafness

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Nov 30, 2016
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:: RCV000150729.5

Allele description [Variation Report for NM_004004.6(GJB2):c.379C>T (p.Arg127Cys)]

NM_004004.6(GJB2):c.379C>T (p.Arg127Cys)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

13q12.11

Genomic location:

Preferred name:

NM_004004.6(GJB2):c.379C>T (p.Arg127Cys)

HGVS:

NC_000013.11:g.20189203G>A
NG_008358.1:g.8773C>T
NM_004004.6:c.379C>TMANE SELECT
NP_003995.2:p.Arg127Cys
LRG_1350t1:c.379C>T
LRG_1350:g.8773C>T
LRG_1350p1:p.Arg127Cys
NC_000013.10:g.20763342G>A
NM_004004.5:c.379C>T

Protein change:

R127C

Links:

dbSNP: rs727503066

NCBI 1000 Genomes Browser:

rs727503066

Molecular consequence:

NM_004004.6:c.379C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Rare genetic deafness
Identifiers:: MedGen: C5680250; Orphanet: 96210

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000198154	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Likely pathogenic (Nov 30, 2016)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 11587277, 17041943, 26896187, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000198154

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Likely pathogenic
(Nov 30, 2016)

germline

clinical testing

PubMed (4)
[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	not provided	3	2	not provided	not provided	not provided	clinical testing

Citations

PubMed

Prevalence and nature of connexin 26 mutations in children with non-syndromic deafness.

Dahl HH, Saunders K, Kelly TM, Osborn AH, Wilcox S, Cone-Wesson B, Wunderlich JL, Du Sart D, Kamarinos M, Gardner RJ, Dennehy S, Williamson R, Vallance N, Mutton P.

Med J Aust. 2001 Aug 20;175(4):191-4. Erratum in: Med J Aust. 2004 Oct 18;181(8):437.

PubMed [citation]

PMID:: 11587277

DNA sequence analysis of GJB2, encoding connexin 26: observations from a population of hearing impaired cases and variable carrier rates, complex genotypes, and ethnic stratification of alleles among controls.

Tang HY, Fang P, Ward PA, Schmitt E, Darilek S, Manolidis S, Oghalai JS, Roa BB, Alford RL.

Am J Med Genet A. 2006 Nov 15;140(22):2401-15. Erratum in: Am J Med Genet A. 2008 Nov 15;146A(22):2979..

PubMed [citation]

PMID:: 17041943
PMCID:: PMC3623690

See all PubMed Citations (4)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000198154.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	3	not provided	not provided	clinical testing	PubMed (4)

Description

The p.Arg127Cys variant in GJB2 has been reported in 6 individuals with hearing loss, including three who were compound heterozygous with another pathogenic GJB 2 variant (Tang 2006, Dahl 2001, Mikstiene 2016, LMM data). This variant has not been identified in large population studies. Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, although additional studies are required to fully esta blish its clinical significance, this variant is likely pathogenic for autosomal recessive hearing loss based on multiple reported affected compound heterozygot es and a significantly higher frequency in affected individuals than in the gene ral population.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		3	not provided	2	not provided

Last Updated: Sep 29, 2024

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