U.S. flag

An official website of the United States government

NM_000166.6(GJB1):c.310A>T (p.Lys104Ter) AND Charcot-Marie-Tooth Neuropathy X

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Nov 3, 2023
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:
RCV003581952.2

Allele description [Variation Report for NM_000166.6(GJB1):c.310A>T (p.Lys104Ter)]

NM_000166.6(GJB1):c.310A>T (p.Lys104Ter)

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.310A>T (p.Lys104Ter)
HGVS:
  • NC_000023.11:g.71224017A>T
  • NG_008357.1:g.13806A>T
  • NM_000166.6:c.310A>TMANE SELECT
  • NM_001097642.3:c.310A>T
  • NP_000157.1:p.Lys104Ter
  • NP_001091111.1:p.Lys104Ter
  • NP_001091111.1:p.Lys104Ter
  • LRG_245t1:c.310A>T
  • LRG_245t2:c.310A>T
  • LRG_245:g.13806A>T
  • LRG_245p1:p.Lys104Ter
  • LRG_245p2:p.Lys104Ter
  • NC_000023.10:g.70443867A>T
  • NM_001097642.2:c.310A>T
Protein change:
K104*
Molecular consequence:
  • NM_000166.6:c.310A>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001097642.3:c.310A>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004244972Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Nov 3, 2023) 		germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

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

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 (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004244972.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This sequence change creates a premature translational stop signal (p.Lys104*) in the GJB1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 180 amino acid(s) of the GJB1 protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with GJB1-related conditions. This variant disrupts a region of the GJB1 protein in which other variant(s) (p.Arg220*) have been determined to be pathogenic (PMID: 7477983, 8162049, 9364054, 21291455). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. 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: Sep 29, 2024