NM_000166.6(GJB1):c.101T>C (p.Met34Thr) AND Charcot-Marie-Tooth Neuropathy X

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 16, 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:: RCV000467465.8

Allele description [Variation Report for NM_000166.6(GJB1):c.101T>C (p.Met34Thr)]

NM_000166.6(GJB1):c.101T>C (p.Met34Thr)

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.101T>C (p.Met34Thr)

HGVS:

NC_000023.11:g.71223808T>C
NG_008357.1:g.13597T>C
NM_000166.6:c.101T>CMANE SELECT
NM_001097642.3:c.101T>C
NP_000157.1:p.Met34Thr
NP_001091111.1:p.Met34Thr
LRG_245t2:c.101T>C
LRG_245:g.13597T>C
LRG_245p2:p.Met34Thr
NC_000023.10:g.70443658T>C
NM_000166.5:c.101T>C

Protein change:

M34T

Links:

dbSNP: rs1060500998

NCBI 1000 Genomes Browser:

rs1060500998

Molecular consequence:

NM_000166.6:c.101T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001097642.3:c.101T>C - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000544768	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 16, 2016)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 9354338, 12460545, 9401007, 8829637, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000544768

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 16, 2016)

germline

clinical testing

PubMed (5)
[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

Changes in permeability caused by connexin 32 mutations underlie X-linked Charcot-Marie-Tooth disease.

Oh S, Ri Y, Bennett MV, Trexler EB, Verselis VK, Bargiello TA.

Neuron. 1997 Oct;19(4):927-38.

PubMed [citation]

PMID:: 9354338

Diverse trafficking abnormalities of connexin32 mutants causing CMTX.

Yum SW, Kleopa KA, Shumas S, Scherer SS.

Neurobiol Dis. 2002 Oct;11(1):43-52.

PubMed [citation]

PMID:: 12460545

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000544768.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

Experimental studies in Xenopus oocytes have shown that this missense change affects the electrophysiological properties of the channel encoded by GJB1, known as Connexin 32 in the literature (PMID: 9354338). Additional experiments in HeLa cells found that this missense change alters the sub-cellular localization of Connexin 32 (PMID: 12460545). For these reasons, this variant has been classified as Pathogenic. This variant has been reported in multiple individuals affected with CMTX (PMID: 9401007. 11571214) and has been observed to co-segregate with disease in an affected family (PMID: 8829637). This variant is not present in population databases (ExAC no frequency). This sequence change replaces methionine with threonine at codon 34 of the GJB1 protein (p.Met34Thr). The methionine residue is moderately conserved and there is a moderate physicochemical difference between methionine and threonine.

#	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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