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NM_004004.6(GJB2):c.557C>A (p.Thr186Lys) AND not specified

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Dec 13, 2023
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:
RCV003490870.1

Allele description [Variation Report for NM_004004.6(GJB2):c.557C>A (p.Thr186Lys)]

NM_004004.6(GJB2):c.557C>A (p.Thr186Lys)

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.557C>A (p.Thr186Lys)
HGVS:
  • NC_000013.11:g.20189025G>T
  • NG_008358.1:g.8951C>A
  • NM_004004.6:c.557C>AMANE SELECT
  • NP_003995.2:p.Thr186Lys
  • LRG_1350t1:c.557C>A
  • LRG_1350:g.8951C>A
  • LRG_1350p1:p.Thr186Lys
  • NC_000013.10:g.20763164G>T
Protein change:
T186K
Molecular consequence:
  • NM_004004.6:c.557C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004241077Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Uncertain significance
(Dec 13, 2023) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

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Summary from all submissions

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

Citations

PubMed

A multicenter study of the frequency and distribution of GJB2 and GJB6 mutations in a large North American cohort.

Putcha GV, Bejjani BA, Bleoo S, Booker JK, Carey JC, Carson N, Das S, Dempsey MA, Gastier-Foster JM, Greinwald JH Jr, Hoffmann ML, Jeng LJ, Kenna MA, Khababa I, Lilley M, Mao R, Muralidharan K, Otani IM, Rehm HL, Schaefer F, Seltzer WK, Spector EB, et al.

Genet Med. 2007 Jul;9(7):413-26.

PubMed [citation]
PMID:
17666888

Audiological Evidence of Frequent Hereditary Mild, Moderate and Moderate-to-Severe Hearing Loss.

Markova T, Alekseeva N, Lalayants M, Ryzhkova O, Shatokhina O, Galeeva N, Bliznetz E, Belov O, Chibisova S, Polyakov A, Tavartkiladze G.

J Pers Med. 2022 Nov 4;12(11). doi: 10.3390/jpm12111843.

PubMed [citation]
PMID:
36579563
PMCID:
PMC9698638

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004241077.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

Variant summary: GJB2 c.557C>A (p.Thr186Lys) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251314 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.557C>A has been reported in the literature in individuals affected with Non-Syndromic Hearing Loss without strong evidence of causality (Putcha_2007, Markova_2022). These reports do not provide unequivocal conclusions about association of the variant with Non-Syndromic Hearing Loss. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 17666888, 36579563). No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.

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

Last Updated: Feb 14, 2024