NM_000166.6(GJB1):c.185G>C (p.Ser62Thr) AND Charcot-Marie-Tooth Neuropathy X

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 12, 2023
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:: RCV003838105.1

Allele description

NM_000166.6(GJB1):c.185G>C (p.Ser62Thr)

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.185G>C (p.Ser62Thr)

HGVS:

NC_000023.11:g.71223892G>C
NG_008357.1:g.13681G>C
NM_000166.6:c.185G>CMANE SELECT
NM_001097642.3:c.185G>C
NP_000157.1:p.Ser62Thr
NP_001091111.1:p.Ser62Thr
NP_001091111.1:p.Ser62Thr
LRG_245t1:c.185G>C
LRG_245t2:c.185G>C
LRG_245:g.13681G>C
LRG_245p1:p.Ser62Thr
LRG_245p2:p.Ser62Thr
NC_000023.10:g.70443742G>C
NM_001097642.2:c.185G>C

Protein change:

S62T

Molecular consequence:

NM_000166.6:c.185G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001097642.3:c.185G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Ercolania kencolesi isolate R1788LI 16S ribosomal RNA gene, partial sequence; mi...
Ercolania kencolesi isolate R1788LI 16S ribosomal RNA gene, partial sequence; mitochondrial
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Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004631070	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 12, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 20942588, 32010055, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004631070

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 12, 2023)

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

Vocal cord paresis and probable X-linked Charcot-Marie-Tooth disease with novel GJB1 mutation.

Li Q, Chen M, Liu K, Lin X, Chui D.

Int J Neurosci. 2010 Nov;120(11):731-4. doi: 10.3109/00207454.2010.513461.

PubMed [citation]

PMID:: 20942588

GJB1 Mutation-A Disease Spectrum: Report of Case Series.

Niu J, Dai Y, Liu M, Li Y, Ding Q, Guan Y, Cui L, Jin L.

Front Neurol. 2019;10:1406. doi: 10.3389/fneur.2019.01406.

PubMed [citation]

PMID:: 32010055
PMCID:: PMC6974795

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV004631070.1

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

Description

This variant disrupts the p.Ser62 amino acid residue in GJB1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 20942588). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 not expected to disrupt GJB1 protein function. 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. This missense change has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 32010055). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 62 of the GJB1 protein (p.Ser62Thr).

#	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: Mar 5, 2024

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