NM_004004.6(GJB2):c.194A>G (p.Tyr65Cys) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 27, 2024
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:: RCV004526604.2

Allele description [Variation Report for NM_004004.6(GJB2):c.194A>G (p.Tyr65Cys)]

NM_004004.6(GJB2):c.194A>G (p.Tyr65Cys)

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.194A>G (p.Tyr65Cys)

HGVS:

NC_000013.11:g.20189388T>C
NG_008358.1:g.8588A>G
NM_004004.6:c.194A>GMANE SELECT
NP_003995.2:p.Tyr65Cys
LRG_1350t1:c.194A>G
LRG_1350:g.8588A>G
LRG_1350p1:p.Tyr65Cys
NC_000013.10:g.20763527T>C
NM_004004.5:c.194A>G
c.194A>G

Protein change:

Y65C

Links:

dbSNP: rs111033203

NCBI 1000 Genomes Browser:

rs111033203

Molecular consequence:

NM_004004.6:c.194A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV005039020	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Mar 27, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 31160754, 26444186, 36048236 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005039020

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Mar 27, 2024)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Consensus interpretation of the p.Met34Thr and p.Val37Ile variants in GJB2 by the ClinGen Hearing Loss Expert Panel.

Shen J, Oza AM, Del Castillo I, Duzkale H, Matsunaga T, Pandya A, Kang HP, Mar-Heyming R, Guha S, Moyer K, Lo C, Kenna M, Alexander JJ, Zhang Y, Hirsch Y, Luo M, Cao Y, Wai Choy K, Cheng YF, Avraham KB, Hu X, Garrido G, et al.

Genet Med. 2019 Nov;21(11):2442-2452. doi: 10.1038/s41436-019-0535-9. Epub 2019 Jun 4.

PubMed [citation]

PMID:: 31160754
PMCID:: PMC7235630

Targeted Droplet-Digital PCR as a Tool for Novel Deletion Discovery at the DFNB1 Locus.

Tayoun AN, Mason-Suares H, Frisella AL, Bowser M, Duffy E, Mahanta L, Funke B, Rehm HL, Amr SS.

Hum Mutat. 2016 Jan;37(1):119-26. doi: 10.1002/humu.22912. Epub 2015 Oct 29.

PubMed [citation]

PMID:: 26444186

See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV005039020.2

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

Description

Variant summary: GJB2 c.194A>G (p.Tyr65Cys) results in a non-conservative amino acid change located in the Connexin, N-terminal (IPR013092) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 251324 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.194A>G has been reported in the literature in individuals affected with Non-Syndromic Hearing Loss (Shen_2019, Tayoun_2015). These data do not allow any conclusion about variant significance. 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: 31160754, 26444186, 36048236). ClinVar contains an entry for this variant (Variation ID: 44727). Based on the evidence outlined above, the variant was classified as uncertain significance.

#	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

Last Updated: Jul 7, 2024

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