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NM_000166.6(GJB1):c.239A>G (p.Gln80Arg) AND Charcot-Marie-Tooth Neuropathy X

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 19, 2024
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:
RCV000466555.5

Allele description [Variation Report for NM_000166.6(GJB1):c.239A>G (p.Gln80Arg)]

NM_000166.6(GJB1):c.239A>G (p.Gln80Arg)

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.239A>G (p.Gln80Arg)
HGVS:
  • NC_000023.11:g.71223946A>G
  • NG_008357.1:g.13735A>G
  • NM_000166.6:c.239A>GMANE SELECT
  • NM_001097642.3:c.239A>G
  • NP_000157.1:p.Gln80Arg
  • NP_001091111.1:p.Gln80Arg
  • LRG_245t2:c.239A>G
  • LRG_245:g.13735A>G
  • LRG_245p2:p.Gln80Arg
  • NC_000023.10:g.70443796A>G
  • NM_000166.5:c.239A>G
  • P08034:p.Gln80Arg
Protein change:
Q80R
Links:
UniProtKB: P08034#VAR_002055; dbSNP: rs879254097
NCBI 1000 Genomes Browser:
rs879254097
Molecular consequence:
  • NM_000166.6:c.239A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001097642.3:c.239A>G - 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
SCV000544779Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Jan 19, 2024)
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

New point mutations and deletions of the connexin 32 gene in X-linked Charcot-Marie-Tooth neuropathy.

Ionasescu V, Searby C, Ionasescu R, Meschino W.

Neuromuscul Disord. 1995 Jul;5(4):297-9.

PubMed [citation]
PMID:
7580242

Screening for mutations in the peripheral myelin genes PMP22, MPZ and Cx32 (GJB1) in Russian Charcot-Marie-Tooth neuropathy patients.

Mersiyanova IV, Ismailov SM, Polyakov AV, Dadali EL, Fedotov VP, Nelis E, Löfgren A, Timmerman V, van Broeckhoven C, Evgrafov OV.

Hum Mutat. 2000;15(4):340-7. Erratum in: Hum Mutat 2000;16(2):175.

PubMed [citation]
PMID:
10737979
See all PubMed Citations (7)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000544779.5

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

Description

This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 80 of the GJB1 protein (p.Gln80Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with Charcot-Marie-Tooth disease (PMID: 7580242, 10737979, 17353473; Invitae). ClinVar contains an entry for this variant (Variation ID: 246096). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt GJB1 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change does not substantially affect GJB1 function (PMID: 15006706). This variant disrupts the p.Gln80 amino acid residue in GJB1. Other variant(s) that disrupt this residue have been observed in individuals with GJB1-related conditions (PMID: 22464564, 28286897), which suggests that this may be a clinically significant amino acid residue. 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: Jan 19, 2025