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NM_000166.5(GJB1):c.77C>T (p.Ser26Leu) AND Charcot-Marie-Tooth Neuropathy X

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jun 25, 2016
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:
RCV000460808.1

Allele description

NM_000166.5(GJB1):c.77C>T (p.Ser26Leu)

Gene:
GJB1:gap junction protein beta 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Xq13.1
Genomic location:
Preferred name:
NM_000166.5(GJB1):c.77C>T (p.Ser26Leu)
HGVS:
  • NC_000023.11:g.71223784C>T
  • NG_008357.1:g.13573C>T
  • NM_000166.5:c.77C>T
  • NM_001097642.2:c.77C>T
  • NP_000157.1:p.Ser26Leu
  • NP_001091111.1:p.Ser26Leu
  • LRG_245t1:c.77C>T
  • LRG_245:g.13573C>T
  • LRG_245p1:p.Ser26Leu
  • NC_000023.10:g.70443634C>T
  • P08034:p.Ser26Leu
Protein change:
S26L
Links:
UniProtKB: P08034#VAR_002025; dbSNP: rs587777876
NCBI 1000 Genomes Browser:
rs587777876
Molecular consequence:
  • NM_001097642.2:c.77C>T - 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

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000544767Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jun 25, 2016) 		germlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000544767.2

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

Description

This sequence change replaces serine with leucine at codon 26 of the GJB1 protein (p.Ser26Leu). The serine residue is highly conserved and there is a large physicochemical difference between serine and leucine. This variant is not present in population databases (rs587777876, ExAC no frequency). This variant has been reported in individuals affected with Charcot-Marie-Tooth disease, type 1X (PMID: 8990008, 25429913). It has also been reported to segregate with disease in affected families (PMID: 9354338, 25802885). ClinVar contains an entry for this variant (Variation ID: 155726) Experimental studies have shown that this variant reduces the pore size of the connexin-32 protein channel which reduces its permeability and impairs proper function (PMID: 9354338). 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: Jul 21, 2018