NM_000166.6(GJB1):c.8G>A (p.Trp3Ter) AND Charcot-Marie-Tooth Neuropathy X

Clinical significance:Pathogenic (Last evaluated: Sep 29, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000654851.1

Allele description [Variation Report for NM_000166.6(GJB1):c.8G>A (p.Trp3Ter)]

NM_000166.6(GJB1):c.8G>A (p.Trp3Ter)

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.8G>A (p.Trp3Ter)
HGVS:
  • NC_000023.11:g.71223715G>A
  • NG_008357.1:g.13504G>A
  • NM_000166.6:c.8G>AMANE SELECT
  • NM_001097642.3:c.8G>A
  • NP_000157.1:p.Trp3Ter
  • NP_001091111.1:p.Trp3Ter
  • LRG_245t2:c.8G>A
  • LRG_245:g.13504G>A
  • LRG_245p2:p.Trp3Ter
  • NC_000023.10:g.70443565G>A
  • NM_000166.5:c.8G>A
Protein change:
W3*
Links:
dbSNP: rs1555936989
NCBI 1000 Genomes Browser:
rs1555936989
Molecular consequence:
  • NM_000166.6:c.8G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001097642.3:c.8G>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000776753Invitaecriteria provided, single submitter
Pathogenic
(Sep 29, 2017)
germlineclinical testing

PubMed (7)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Altered trafficking of mutant connexin32.

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

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

PubMed [citation]
PMID:
9364054
PMCID:
PMC6573613

New connexin32 mutations associated with X-linked Charcot-Marie-Tooth disease.

Bone LJ, Dahl N, Lensch MW, Chance PF, Kelly T, Le Guern E, Magi S, Parry G, Shapiro H, Wang S, et al.

Neurology. 1995 Oct;45(10):1863-6.

PubMed [citation]
PMID:
7477983
See all PubMed Citations (7)

Details of each submission

From Invitae, SCV000776753.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (7)

Description

This sequence change results in a premature translational stop signal in the GJB1 gene (p.Trp3*). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 281 amino acids (99%) of the GJB1 protein. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several individuals affected with Charcot-Marie-Tooth disease, type X1 (PMID: 22464564, 27088055, 27804109). Several truncations downstream of this variant (p.Tyr65* and p.Arg220*) have been determined to be pathogenic (PMID: 224645664, 7477983, 9364054). This suggests that deletion of this region of the GJB1 protein is causative of disease. For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 27, 2021

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