NM_000166.6(GJB1):c.-17G>A AND Charcot-Marie-Tooth Neuropathy X

Clinical significance:Pathogenic (Last evaluated: Jan 7, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000470682.5

Allele description [Variation Report for NM_000166.6(GJB1):c.-17G>A]

NM_000166.6(GJB1):c.-17G>A

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.-17G>A
HGVS:
  • NC_000023.11:g.71223335G>A
  • NG_008357.1:g.13124G>A
  • NM_000166.6:c.-17G>AMANE SELECT
  • NM_001097642.3:c.-16-357G>A
  • LRG_245t2:c.-17G>A
  • LRG_245:g.13124G>A
  • NC_000023.10:g.70443185G>A
  • NM_000166.5:c.-17G>A
Links:
dbSNP: rs879254047
NCBI 1000 Genomes Browser:
rs879254047
Molecular consequence:
  • NM_000166.6:c.-17G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001097642.3:c.-16-357G>A - intron variant - [Sequence Ontology: SO:0001627]

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
SCV000544774Invitaecriteria provided, single submitter
Pathogenic
(Jan 7, 2020)
germlineclinical testing

PubMed (8)
[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

A novel mutation in the nerve-specific 5'UTR of the GJB1 gene causes X-linked Charcot-Marie-Tooth disease.

Murphy SM, Polke J, Manji H, Blake J, Reiniger L, Sweeney M, Houlden H, Brandner S, Reilly MM.

J Peripher Nerv Syst. 2011 Mar;16(1):65-70. doi: 10.1111/j.1529-8027.2011.00321.x.

PubMed [citation]
PMID:
21504505

Hand weakness in Charcot-Marie-Tooth disease 1X.

Arthur-Farraj PJ, Murphy SM, Laura M, Lunn MP, Manji H, Blake J, Ramdharry G, Fox Z, Reilly MM.

Neuromuscul Disord. 2012 Jul;22(7):622-6. doi: 10.1016/j.nmd.2012.02.008. Epub 2012 Mar 28.

PubMed [citation]
PMID:
22464564
PMCID:
PMC3657175
See all PubMed Citations (8)

Details of each submission

From Invitae, SCV000544774.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (8)

Description

This sequence change falls in the 5' UTR of the GJB1 gene. It does not change the encoded amino acid sequence of the GJB1 protein, but It falls at the last nucleotide of exon 1 of the GJB1 non-coding sequence. Frequency data for this variant from the ExAC database is not available, and its frequency in the general population is not known. This variant has been reported to segregate with CMT1X in three families (PMID: 21504505, 28283593). It has also been reported in multiple individuals affected with CMT1X (PMID: 22464564, 28283593, 26392352, 28768847, Invitae database). This variant is also known as c.-373G>A in the literature. ClinVar contains an entry for this variant (Variation ID: 246014). Nucleotide substitutions within the consensus splice site are relatively common causes of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of nucleotide changes on mRNA splicing suggest that this variant may alter mRNA splicing, but this prediction has not been confirmed by published transcriptional studies. 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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