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NM_004004.6(GJB2):c.334_335del (p.Lys112fs) AND Autosomal recessive nonsyndromic hearing loss 1A

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Feb 1, 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:
RCV002222422.2

Allele description

NM_004004.6(GJB2):c.334_335del (p.Lys112fs)

Gene:
GJB2:gap junction protein beta 2 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
13q12.11
Genomic location:
Preferred name:
NM_004004.6(GJB2):c.334_335del (p.Lys112fs)
HGVS:
  • NC_000013.10:g.20763386_20763387del
  • NC_000013.11:g.20189248_20189249del
  • NG_008358.1:g.8728_8729del
  • NM_004004.6:c.334_335delMANE SELECT
  • NP_003995.2:p.Lys112fs
  • LRG_1350t1:c.334_335del
  • LRG_1350:g.8728_8729del
  • LRG_1350p1:p.Lys112fs
  • NC_000013.10:g.20763386_20763387del
  • NC_000013.10:g.20763387_20763388del
  • NC_000013.10:g.20763387_20763388delTT
  • NC_000013.11:g.20189248_20189249delTT
  • NM_004004.5:c.333_334delAA
  • NM_004004.5:c.334_335delAA
  • NM_004004.6:c.334_335delAAMANE SELECT
  • p.Lys112Glufs*2
  • p.Lys112fs
Protein change:
K112fs
Links:
dbSNP: rs756484720
NCBI 1000 Genomes Browser:
rs756484720
Molecular consequence:
  • NM_004004.6:c.334_335del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Autosomal recessive nonsyndromic hearing loss 1A (DFNB1A)
Synonyms:
Deafness nonsyndromic, Connexin 26 linked; Deafness, autosomal recessive 1A; DFNB 1 Nonsyndromic Hearing Loss and Deafness; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0009076; MedGen: C2673759; Orphanet: 90636; OMIM: 220290

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002500583Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Pathogenic
(Mar 22, 2022) 		germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Citation Link,

SCV005051795Laboratory of Medical Genetics, National & Kapodistrian University of Athens
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Feb 1, 2024) 		germlinecuration

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenonot providednot providednot providednot providednot providedcuration
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Novel mutations in the connexin 26 gene (GJB2) that cause autosomal recessive (DFNB1) hearing loss.

Kelley PM, Harris DJ, Comer BC, Askew JW, Fowler T, Smith SD, Kimberling WJ.

Am J Hum Genet. 1998 Apr;62(4):792-9.

PubMed [citation]
PMID:
9529365
PMCID:
PMC1377046

Vestibular dysfunction in DFNB1 deafness.

Dodson KM, Blanton SH, Welch KO, Norris VW, Nuzzo RL, Wegelin JA, Marin RS, Nance WE, Pandya A, Arnos KS.

Am J Med Genet A. 2011 May;155A(5):993-1000. doi: 10.1002/ajmg.a.33828. Epub 2011 Apr 4.

PubMed [citation]
PMID:
21465647
PMCID:
PMC3080433
See all PubMed Citations (6)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002500583.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

Variant summary: GJB2 c.334_335delAA (p.Lys112GlufsX2) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 8e-06 in 250258 control chromosomes. c.334_335delAA has been reported in the literature in multiple individuals affected with Autosomal Recessive Non-Syndromic Hearing Loss, and has been shown to segregate with disease in several families. Seven clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Laboratory of Medical Genetics, National & Kapodistrian University of Athens, SCV005051795.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcuration PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenonot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jun 17, 2024