NM_000166.6(GJB1):c.704T>G (p.Phe235Cys) AND Charcot-Marie-Tooth Neuropathy X Type 1

Clinical significance:Likely benign (Last evaluated: May 28, 2019)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
4 submissions [Details]
Record status:
current
Accession:
RCV000011195.9

Allele description [Variation Report for NM_000166.6(GJB1):c.704T>G (p.Phe235Cys)]

NM_000166.6(GJB1):c.704T>G (p.Phe235Cys)

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.704T>G (p.Phe235Cys)
HGVS:
  • NC_000023.11:g.71224411T>G
  • NG_008357.1:g.14200T>G
  • NM_000166.6:c.704T>GMANE SELECT
  • NM_001097642.3:c.704T>G
  • NP_000157.1:p.Phe235Cys
  • NP_001091111.1:p.Phe235Cys
  • LRG_245t2:c.704T>G
  • LRG_245:g.14200T>G
  • LRG_245p2:p.Phe235Cys
  • NC_000023.10:g.70444261T>G
  • NM_000166.5:c.704T>G
  • P08034:p.Phe235Cys
Protein change:
F235C; PHE235CYS
Links:
UniProtKB: P08034#VAR_002135; OMIM: 304040.0020; dbSNP: rs104894825
NCBI 1000 Genomes Browser:
rs104894825
Molecular consequence:
  • NM_000166.6:c.704T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001097642.3:c.704T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Charcot-Marie-Tooth Neuropathy X Type 1 (CMTX1)
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

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000031422OMIMno assertion criteria providedPathogenic
(May 1, 2005)
germlineliterature only

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

SCV000040510GeneReviewsno assertion criteria providedpathologic
(Apr 15, 2010)
not providedcuration

SCV000482715Illumina Clinical Services Laboratory,Illuminacriteria provided, single submitter
Likely benign
(Apr 28, 2017)
germlineclinical testing

PubMed (10)
[See all records that cite these PMIDs]

Citation Link,

SCV001141917Mendelicscriteria provided, single submitter
Likely benign
(May 28, 2019)
unknownclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providednot providednot providednot providednot providednot providednot providednot providedcuration
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

XLID-causing mutations and associated genes challenged in light of data from large-scale human exome sequencing.

Piton A, Redin C, Mandel JL.

Am J Hum Genet. 2013 Aug 8;93(2):368-83. doi: 10.1016/j.ajhg.2013.06.013. Epub 2013 Jul 18. Erratum in: Am J Hum Genet. 2013 Aug 8;93(2):406.

PubMed [citation]
PMID:
23871722
PMCID:
PMC3738825

X-linked dominant Charcot-Marie-Tooth disease with connexin 32 (Cx32) mutations in Koreans.

Kim Y, Choi KG, Park KD, Lee KS, Chung KW, Choi BO.

Clin Genet. 2012 Feb;81(2):142-9. doi: 10.1111/j.1399-0004.2011.01642.x. Epub 2011 Mar 1.

PubMed [citation]
PMID:
21291455
See all PubMed Citations (10)

Details of each submission

From OMIM, SCV000031422.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In a girl with a severe early-onset form of X-linked CMT (302800), Liang et al. (2005) identified a 766T-G transversion in the GJB1 gene, resulting in a phe235-to-cys (F235C) substitution in the carboxy tail domain of the protein. The mutation was not identified in 50 control chromosomes. The patient's asymptomatic mother also carried the mutation, but Southern blot analysis showed preferential inactivation of the mutant X-chromosome by a ratio of approximately 9 to 1. Functional expression studies demonstrated that cells with the F235C mutant protein had normal plasma membrane expression of the channel protein, but showed a reduction of the resting membrane potential of more than 40 mV, with a decrease in the threshold of activation. Cells expressing the mutant protein also showed decreased viability compared to wildtype. Liang et al. (2005) concluded that the propensity of the F235C hemichannels to be open at resting membrane potential ('leaky channel') adversely affected cell viability, thus resulting in a severe phenotype. Similar in vitro findings had been reported for another GJB1 mutation (S85C; 304040.0014).

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

From GeneReviews, SCV000040510.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

Converted during submission to Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1not providednot providednot providednot providedAssert pathogenicitynot providednot providednot providednot provided

From Illumina Clinical Services Laboratory,Illumina, SCV000482715.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (10)

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.

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

From Mendelics, SCV001141917.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 27, 2021

Support Center