NM_000166.6(GJB1):c.542T>C (p.Val181Ala) AND Charcot-Marie-Tooth Neuropathy X

Clinical significance:Uncertain significance (Last evaluated: May 15, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001350409.1

Allele description [Variation Report for NM_000166.6(GJB1):c.542T>C (p.Val181Ala)]

NM_000166.6(GJB1):c.542T>C (p.Val181Ala)

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.542T>C (p.Val181Ala)
HGVS:
  • NC_000023.11:g.71224249T>C
  • NG_008357.1:g.14038T>C
  • NM_000166.6:c.542T>CMANE SELECT
  • NM_001097642.3:c.542T>C
  • NP_000157.1:p.Val181Ala
  • NP_001091111.1:p.Val181Ala
  • LRG_245t2:c.542T>C
  • LRG_245:g.14038T>C
  • LRG_245p2:p.Val181Ala
  • NC_000023.10:g.70444099T>C
  • NM_000166.5:c.542T>C
Protein change:
V181A
Links:
dbSNP: rs876661252
NCBI 1000 Genomes Browser:
rs876661252
Molecular consequence:
  • NM_000166.6:c.542T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001097642.3:c.542T>C - missense variant - [Sequence Ontology: SO:0001583]

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
SCV001544808Invitaecriteria provided, single submitter
Uncertain significance
(May 15, 2020)
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

Pathogenesis of X-linked Charcot-Marie-Tooth disease: differential effects of two mutations in connexin 32.

Abrams CK, Freidin M, Bukauskas F, Dobrenis K, Bargiello TA, Verselis VK, Bennett MV, Chen L, Sahenk Z.

J Neurosci. 2003 Nov 19;23(33):10548-58.

PubMed [citation]
PMID:
14627639
PMCID:
PMC4513672

Connexin32 and X-linked Charcot-Marie-Tooth disease.

Bone LJ, DeschĂȘnes SM, Balice-Gordon RJ, Fischbeck KH, Scherer SS.

Neurobiol Dis. 1997;4(3-4):221-30. Review.

PubMed [citation]
PMID:
9361298
See all PubMed Citations (7)

Details of each submission

From Invitae, SCV001544808.1

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

Description

This sequence change replaces valine with alanine at codon 181 of the GJB1 protein (p.Val181Ala). The valine residue is highly conserved and there is a small physicochemical difference between valine and alanine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 14627639). ClinVar contains an entry for this variant (Variation ID: 637559). This variant has been reported to affect GJB1 protein function (PMID: 14627639). This variant disrupts the p.Val181 amino acid residue in GJB1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9361298, 17100997, 19259128, 21692908, 25947624). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Nov 27, 2021

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