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NM_004004.6(GJB2):c.176G>A (p.Gly59Asp) AND Rare genetic deafness

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Oct 23, 2014
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:
RCV000150733.5

Allele description [Variation Report for NM_004004.6(GJB2):c.176G>A (p.Gly59Asp)]

NM_004004.6(GJB2):c.176G>A (p.Gly59Asp)

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.176G>A (p.Gly59Asp)
HGVS:
  • NC_000013.11:g.20189406C>T
  • NG_008358.1:g.8570G>A
  • NM_004004.6:c.176G>AMANE SELECT
  • NP_003995.2:p.Gly59Asp
  • LRG_1350t1:c.176G>A
  • LRG_1350:g.8570G>A
  • LRG_1350p1:p.Gly59Asp
  • NC_000013.10:g.20763545C>T
  • NM_004004.5:c.176G>A
Protein change:
G59D
Links:
dbSNP: rs104894404
NCBI 1000 Genomes Browser:
rs104894404
Molecular consequence:
  • NM_004004.6:c.176G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000198166Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(LMM Criteria)		Likely pathogenic
(Oct 23, 2014) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided11not providednot providednot providedclinical testing

Citations

PubMed

A connexin 26 mutation causes a syndrome of sensorineural hearing loss and palmoplantar hyperkeratosis (MIM 148350).

Heathcote K, Syrris P, Carter ND, Patton MA.

J Med Genet. 2000 Jan;37(1):50-1.

PubMed [citation]
PMID:
10633135
PMCID:
PMC1734451

GJB2 mutations in patients with non-syndromic hearing loss from Northeastern Hungary.

Tóth T, Kupka S, Haack B, Riemann K, Braun S, Fazakas F, Zenner HP, Muszbek L, Blin N, Pfister M, Sziklai I.

Hum Mutat. 2004 Jun;23(6):631-2.

PubMed [citation]
PMID:
15146474
See all PubMed Citations (5)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000198166.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (5)

Description

The p.Gly59Asp variant in GJB2 has not been reported in individuals with hearing loss or in large population studies. However, several missense variants at the same amino acid position (p.Gly59Ala, p.Gly59Val, p.Gly59Arg, p.Gly59Ser) have b een reported in individuals with sensorineural hearing loss with or without palm oplantar hyperkeratosis. These variants were observed to segregate in affected f amily members in several pedigrees in an autosomal dominant pattern (Heathcote 2 000, Toth 2004, Leonard 2005, Alexandrino 2005), and in one study the variant wa s confirmed to have occurred de novo (Leonard 2005). This information strongly s uggests that variants at this amino acid residue are not tolerated. In addition, computational prediction tools and conservation analysis suggest that the p.Gly 59Asp variant may impact the protein. In summary, although additional studies ar e required to fully establish its clinical significance, this variant is likely pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided1not provided1not provided

Last Updated: Dec 24, 2023