NM_000166.6(GJB1):c.*15C>T AND Charcot-Marie-Tooth Neuropathy X

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 4, 2019
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:: RCV001057812.9

Allele description [Variation Report for NM_000166.6(GJB1):c.*15C>T]

NM_000166.6(GJB1):c.*15C>T

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.*15C>T

HGVS:

NC_000023.11:g.71224574C>T
NG_008357.1:g.14363C>T
NM_000166.6:c.*15C>TMANE SELECT
NM_001097642.3:c.*15C>T
LRG_245t2:c.*15C>T
LRG_245:g.14363C>T
NC_000023.10:g.70444424C>T
NM_000166.5:c.*15C>T

Links:

dbSNP: rs1057520778

NCBI 1000 Genomes Browser:

rs1057520778

Molecular consequence:

NM_000166.6:c.*15C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001097642.3:c.*15C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]

Condition(s)

Name:: Charcot-Marie-Tooth Neuropathy X
Identifiers:: MedGen: CN118851

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001222327	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 4, 2019)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 28283593, 29236290, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001222327

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 4, 2019)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations in noncoding regions of GJB1 are a major cause of X-linked CMT.

Tomaselli PJ, Rossor AM, Horga A, Jaunmuktane Z, Carr A, Saveri P, Piscosquito G, Pareyson D, Laura M, Blake JC, Poh R, Polke J, Houlden H, Reilly MM.

Neurology. 2017 Apr 11;88(15):1445-1453. doi: 10.1212/WNL.0000000000003819. Epub 2017 Mar 10.

PubMed [citation]

PMID:: 28283593
PMCID:: PMC5386440

An 8-generation family with X-linked Charcot-Marie-Tooth: Confirmation Of the pathogenicity Of a 3' untranslated region mutation in GJB1 and its clinical features.

Chen DH, Ma M, Scavina M, Blue E, Wolff J, Karna P, Dorschner MO, Raskind WH, Bird TD.

Muscle Nerve. 2018 May;57(5):859-862. doi: 10.1002/mus.26037. Epub 2017 Dec 28.

PubMed [citation]

PMID:: 29236290
PMCID:: PMC5910283

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001222327.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This variant occurs in a non-coding region of the GJB1 gene. It does not change the encoded amino acid sequence of the GJB1 protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with Charcot-Marie-Tooth (CMT) disease and was observed¬†to segregate with CMT in a large family¬†(PMID: 28283593, 29236290). ClinVar contains an entry for this variant (Variation ID: 379903). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of this non-coding change is currently unknown. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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