NM_000166.6(GJB1):c.622G>A (p.Glu208Lys) AND Inborn genetic diseases

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 10, 2020
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:: RCV002367715.3

Allele description [Variation Report for NM_000166.6(GJB1):c.622G>A (p.Glu208Lys)]

NM_000166.6(GJB1):c.622G>A (p.Glu208Lys)

Gene:

GJB1:gap junction protein beta 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xq13.1

Genomic location:

Preferred name:

NM_000166.6(GJB1):c.622G>A (p.Glu208Lys)

HGVS:

NC_000023.11:g.71224329G>A
NG_008357.1:g.14118G>A
NM_000166.6:c.622G>AMANE SELECT
NM_001097642.3:c.622G>A
NP_000157.1:p.Glu208Lys
NP_001091111.1:p.Glu208Lys
LRG_245t2:c.622G>A
LRG_245:g.14118G>A
LRG_245p2:p.Glu208Lys
NC_000023.10:g.70444179G>A
NM_000166.5:c.622G>A

Protein change:

E208K

Links:

dbSNP: rs1555937270

NCBI 1000 Genomes Browser:

rs1555937270

Molecular consequence:

NM_000166.6:c.622G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001097642.3:c.622G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Inborn genetic diseases
Identifiers:: MeSH: D030342; MedGen: C0950123

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
SCV002659810	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Nov 10, 2020)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 10848620, 15006706, 29629536, 8162049, 9364054, 9592087 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002659810

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Nov 10, 2020)

germline

clinical testing

PubMed (6)
[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

Intracellular transport, assembly, and degradation of wild-type and disease-linked mutant gap junction proteins.

VanSlyke JK, Deschenes SM, Musil LS.

Mol Biol Cell. 2000 Jun;11(6):1933-46.

PubMed [citation]

PMID:: 10848620
PMCID:: PMC14894

Functional analysis of connexin-32 mutants associated with X-linked dominant Charcot-Marie-Tooth disease.

Wang HL, Chang WT, Yeh TH, Wu T, Chen MS, Wu CY.

Neurobiol Dis. 2004 Mar;15(2):361-70.

PubMed [citation]

PMID:: 15006706

See all PubMed Citations (6)

Details of each submission

From Ambry Genetics, SCV002659810.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

The p.E208K pathogenic mutation (also known as c.622G>A), located in coding exon 1 of the GJB1 gene, results from a G to A substitution at nucleotide position 622. The glutamic acid at codon 208 is replaced by lysine, an amino acid with similar properties. This alteration has been detected in individuals with Charcot-Marie-Tooth neuropathy and has been reported to segregate with disease in families (Fairweather N et al. Hum Mol Genet, 1994 Jan;3:29-34; Feng SY et al. J Clin Neurol, 2018 Apr;14:261-263). Additionally, studies have shown that this alteration affects the function of the GJB1 protein (Deschênes SM et al. J Neurosci, 1997 Dec;17:9077-84; Ressot C et al. J Neurosci, 1998 Jun;18:4063-75; VanSlyke JK et al. Mol Biol Cell, 2000 Jun;11:1933-46; Wang HL et al. Neurobiol Dis, 2004 Mar;15:361-70). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

#	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: Oct 8, 2024

ClinVar

Relating variation to medicine