NM_000166.6(GJB1):c.424C>T (p.Arg142Trp) AND Charcot-Marie-Tooth disease X-linked dominant 1

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Sep 22, 2024
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:: RCV000011176.7

Allele description [Variation Report for NM_000166.6(GJB1):c.424C>T (p.Arg142Trp)]

NM_000166.6(GJB1):c.424C>T (p.Arg142Trp)

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.424C>T (p.Arg142Trp)

HGVS:

NC_000023.11:g.71224131C>T
NG_008357.1:g.13920C>T
NM_000166.6:c.424C>TMANE SELECT
NM_001097642.2:c.424C>T
NM_001097642.3:c.424C>T
NP_000157.1:p.Arg142Trp
NP_001091111.1:p.Arg142Trp
LRG_245t1:c.424C>T
LRG_245t2:c.424C>T
LRG_245:g.13920C>T
LRG_245p2:p.Arg142Trp
NC_000023.10:g.70443981C>T
NM_000166.5:c.424C>T
P08034:p.Arg142Trp
p.(Arg142Trp)

Protein change:

R142W; ARG142TRP

Links:

UniProtKB: P08034#VAR_002086; OMIM: 304040.0001; dbSNP: rs104894810

NCBI 1000 Genomes Browser:

rs104894810

Molecular consequence:

NM_000166.6:c.424C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001097642.3:c.424C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Charcot-Marie-Tooth disease X-linked dominant 1
Synonyms:: CHARCOT-MARIE-TOOTH NEUROPATHY, X-LINKED, 1; CMTX 1; Charcot-Marie-Tooth peroneal muscular atrophy, X-linked; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010549; MedGen: C0393808; Orphanet: 101075; OMIM: 302800

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000031403	OMIM	no assertion criteria provided	Pathogenic (Dec 24, 1993)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000999824	Center of Genomic medicine, Geneva, University Hospital of Geneva	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Aug 3, 2018)	maternal	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005374319	Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Sep 22, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000031403

OMIM

no assertion criteria provided

Pathogenic
(Dec 24, 1993)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

SCV000999824

Center of Genomic medicine, Geneva, University Hospital of Geneva

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Aug 3, 2018)

maternal

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV005374319

Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Sep 22, 2024)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	maternal	yes	2	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Connexin mutations in X-linked Charcot-Marie-Tooth disease.

Bergoffen J, Scherer SS, Wang S, Scott MO, Bone LJ, Paul DL, Chen K, Lensch MW, Chance PF, Fischbeck KH.

Science. 1993 Dec 24;262(5142):2039-42.

PubMed [citation]

PMID:: 8266101

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From OMIM, SCV000031403.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a family with X-linked Charcot-Marie-Tooth disease (302800), Bergoffen et al. (1993) found a C-to-T transition in codon 142 of the CX32 gene, resulting in substitution of tryptophan for arginine.

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

From Center of Genomic medicine, Geneva, University Hospital of Geneva, SCV000999824.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	maternal	yes	not provided	not provided	not provided		2	not provided	not provided	not provided

From Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, SCV005374319.1

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

#	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 13, 2024

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