NM_004004.6(GJB2):c.499G>A (p.Val167Met) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Sep 16, 2020
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:: RCV000991849.4

Allele description [Variation Report for NM_004004.6(GJB2):c.499G>A (p.Val167Met)]

NM_004004.6(GJB2):c.499G>A (p.Val167Met)

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.499G>A (p.Val167Met)

HGVS:

NC_000013.11:g.20189083C>T
NG_008358.1:g.8893G>A
NM_004004.6:c.499G>AMANE SELECT
NP_003995.2:p.Val167Met
LRG_1350t1:c.499G>A
LRG_1350:g.8893G>A
LRG_1350p1:p.Val167Met
NC_000013.10:g.20763222C>T
NM_004004.5:c.499G>A
P29033:p.Val167Met
c.499G>A

Protein change:

V167M

Links:

UniProtKB: P29033#VAR_023612; dbSNP: rs111033360

NCBI 1000 Genomes Browser:

rs111033360

Molecular consequence:

NM_004004.6:c.499G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001143673	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Uncertain significance (Jun 24, 2019)	germline	clinical testing	PubMed (13) [See all records that cite these PMIDs] 17666888, 25162826, 17426645, 25087612, 25388846, 14722929, 17357124, 27534436, 26046157, 29773520, 21392827, 27501294, 26467025
SCV001986168	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Sep 16, 2020)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001143673

Athena Diagnostics

criteria provided, single submitter

(Athena Diagnostics Criteria)

Uncertain significance
(Jun 24, 2019)

germline

clinical testing

PubMed (13)
[See all records that cite these PMIDs]

SCV001986168

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Sep 16, 2020)

germline

clinical testing

Citation Link

Help

Summary from all submissions

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

Sequencing of GJB2 in Cameroonians and Black South Africans and comparison to 1000 Genomes Project Data Support Need to Revise Strategy for Discovery of Nonsyndromic Deafness Genes in Africans.

Bosch J, Noubiap JJ, Dandara C, Makubalo N, Wright G, Entfellner JB, Tiffin N, Wonkam A.

OMICS. 2014 Nov;18(11):705-10. doi: 10.1089/omi.2014.0063. Epub 2014 Aug 27.

PubMed [citation]

PMID:: 25162826
PMCID:: PMC5206689

See all PubMed Citations (13)

Details of each submission

From Athena Diagnostics, SCV001143673.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (13)

#	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

From GeneDx, SCV001986168.2

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

Description

Observed in multiple individuals with apparent autosomal recessive nonsyndromic hearing loss in published literature; however, the majority of these individuals did not harbor another variant in the GJB2 gene (Gasmelseed et al., 2004; Bosch et al., 2014; Wonkam et al., 2015; Shi et al., 2016; Tingang et al., 2019); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 17426645, 25388846, 17666888, 30245029, 31731535, 25087612, 25162826, 27534436, 26046157, 14722929)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 7, 2024

ClinVar

Relating variation to medicine