NM_000166.6(GJB1):c.622G>A (p.Glu208Lys) AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Jan 23, 2023
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:: RCV000518825.21

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]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000613495	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Pathogenic (Jan 30, 2017)	germline	clinical testing	PubMed (18) [See all records that cite these PMIDs] 10586261, 8162049, 27549087, 21692908, 17353473, 14960772, 16912585, 25429913, 21291455, 26454100, 10646523, 10586291, 10848620, 15006706, 9364054, 10737979, 10234007, 26467025
SCV001500644	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Oct 1, 2020)	germline	clinical testing	Citation Link,
SCV003805347	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Jan 23, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000613495

Athena Diagnostics

criteria provided, single submitter

(Athena Diagnostics Criteria)

Pathogenic
(Jan 30, 2017)

germline

clinical testing

PubMed (18)
[See all records that cite these PMIDs]

SCV001500644

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Pathogenic
(Oct 1, 2020)

germline

clinical testing

Citation Link,

SCV003805347

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Jan 23, 2023)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Genotype/phenotype correlations in X-linked dominant Charcot-Marie-Tooth disease.

Hahn AF, Bolton CF, White CM, Brown WF, Tuuha SE, Tan CC, Ainsworth PJ.

Ann N Y Acad Sci. 1999 Sep 14;883:366-82.

PubMed [citation]

PMID:: 10586261

Mutations in the connexin 32 gene in X-linked dominant Charcot-Marie-Tooth disease (CMTX1)

Fairweather N, Bell C, Cochrane S, Chelly J, Wang S, Mostacciuolo ML, Monaco AP, Haites NE.

Hum Mol Genet. 1994 Jan;3(1):29-34. Erratum in: Hum Mol Genet 1994 Jun;3(6):1034.

PubMed [citation]

PMID:: 8162049

See all PubMed Citations (18)

Details of each submission

From Athena Diagnostics, SCV000613495.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (18)

#	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 CeGaT Center for Human Genetics Tuebingen, SCV001500644.19

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

#	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		1	not provided	not provided	not provided

From GeneDx, SCV003805347.1

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

Description

Published functional studies demonstrate the variant results in impaired intracelluar trafficking of the protein to the plasma membrane (Deschenes et al., 1997; Wang et al., 2004); Not observed in large population cohorts (gnomAD); Missense variants in this gene are often considered pathogenic (HGMD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31372974, 32047472, 9592087, 9364054, 10848620, 17646144, 26454100, 15006706, 29629536, 27549087, 8162049, 14960772)

#	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: Jun 17, 2024

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