NM_004004.6(GJB2):c.583A>G (p.Met195Val) AND GJB2-related disorder

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jun 1, 2024
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV004530262.2

Allele description [Variation Report for NM_004004.6(GJB2):c.583A>G (p.Met195Val)]

NM_004004.6(GJB2):c.583A>G (p.Met195Val)

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.583A>G (p.Met195Val)

HGVS:

NC_000013.11:g.20188999T>C
NG_008358.1:g.8977A>G
NM_004004.6:c.583A>GMANE SELECT
NP_003995.2:p.Met195Val
LRG_1350t1:c.583A>G
LRG_1350:g.8977A>G
LRG_1350p1:p.Met195Val
NC_000013.10:g.20763138T>C
NC_000013.10:g.20763138T>C
NM_004004.5:c.583A>G
NM_004004.6(GJB2):c.583A>GMANE SELECT

Protein change:

M195V

Links:

dbSNP: rs532203068

NCBI 1000 Genomes Browser:

rs532203068

Molecular consequence:

NM_004004.6:c.583A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: GJB2-related disorder
Synonyms:: GJB2-related condition; GJB2-related disorders
Identifiers:

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004714870	PreventionGenetics, part of Exact Sciences	no assertion criteria provided	Likely pathogenic (Jun 1, 2024)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004714870

PreventionGenetics, part of Exact Sciences

no assertion criteria provided

Likely pathogenic
(Jun 1, 2024)

germline

clinical testing

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

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV004714870.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

The GJB2 c.583A>G variant is predicted to result in the amino acid substitution p.Met195Val. This variant has been reported in the compound heterozygous state in multiple individuals with hearing loss (Tsukada et al. 2010. PubMed ID: 20497192; Wang et al. 2021. PubMed ID: 33597575; Minami et al. 2013. PubMed ID: 24013081). This variant is reported in 0.022% of alleles in individuals of East Asian descent in gnomAD and is interpreted as likely pathogenic by the ClinGen Hearing Loss Variant Curation Expert Panel (https://www.ncbi.nlm.nih.gov/clinvar/variation/225375/). This variant is interpreted as likely pathogenic.

#	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: May 25, 2025

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