NM_000166.6(GJB1):c.183dup (p.Ser62fs) AND Charcot-Marie-Tooth Neuropathy X

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 21, 2018
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:: RCV000549070.9

Allele description [Variation Report for NM_000166.6(GJB1):c.183dup (p.Ser62fs)]

NM_000166.6(GJB1):c.183dup (p.Ser62fs)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

Xq13.1

Genomic location:

Preferred name:

NM_000166.6(GJB1):c.183dup (p.Ser62fs)

HGVS:

NC_000023.11:g.71223890dup
NG_008357.1:g.13679dup
NM_000166.6:c.183dupMANE SELECT
NM_001097642.3:c.183dup
NP_000157.1:p.Ser62fs
NP_001091111.1:p.Ser62fs
LRG_245t2:c.183dup
LRG_245:g.13679dup
LRG_245p2:p.Ser62fs
NC_000023.10:g.70443739_70443740insC
NC_000023.10:g.70443740dup
NM_000166.5:c.183dupC

Protein change:

S62fs

Links:

dbSNP: rs1555937084

NCBI 1000 Genomes Browser:

rs1555937084

Molecular consequence:

NM_000166.6:c.183dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001097642.3:c.183dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Charcot-Marie-Tooth Neuropathy X
Identifiers:: MedGen: CN118851

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000658902	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 21, 2018)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 8162049, 9364054, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000658902

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 21, 2018)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

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

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

Altered trafficking of mutant connexin32.

Deschênes SM, Walcott JL, Wexler TL, Scherer SS, Fischbeck KH.

J Neurosci. 1997 Dec 1;17(23):9077-84.

PubMed [citation]

PMID:: 9364054
PMCID:: PMC6573613

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000658902.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This variant is not present in population databases (ExAC no frequency). For these reasons, this variant has been classified as Pathogenic. A different truncation downstream of this variant (p.Arg220*) has been determined to be pathogenic (PMID: 8162049, 9364054). This suggests that deletion of this region of the GJB1 protein is causative of disease. This variant has not been reported in the literature in individuals with GJB1-related disease.¬†ClinVar contains an entry for this variant (Variation ID:¬†477590). This sequence change results in a premature translational stop signal in the GJB1 gene (p.Ser62Glnfs*5). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 222 amino acids (~78%) of the GJB1 protein.

#	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: Sep 29, 2024

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