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NM_000166.6(GJB1):c.413G>C (p.Ser138Thr) AND Charcot-Marie-Tooth Neuropathy X

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
May 28, 2022
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:
RCV002824268.3

Allele description [Variation Report for NM_000166.6(GJB1):c.413G>C (p.Ser138Thr)]

NM_000166.6(GJB1):c.413G>C (p.Ser138Thr)

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.413G>C (p.Ser138Thr)
HGVS:
  • NC_000023.11:g.71224120G>C
  • NG_008357.1:g.13909G>C
  • NM_000166.6:c.413G>CMANE SELECT
  • NM_001097642.3:c.413G>C
  • NP_000157.1:p.Ser138Thr
  • NP_001091111.1:p.Ser138Thr
  • NP_001091111.1:p.Ser138Thr
  • LRG_245t1:c.413G>C
  • LRG_245t2:c.413G>C
  • LRG_245:g.13909G>C
  • LRG_245p1:p.Ser138Thr
  • LRG_245p2:p.Ser138Thr
  • NC_000023.10:g.70443970G>C
  • NM_001097642.2:c.413G>C
Protein change:
S138T
Molecular consequence:
  • NM_000166.6:c.413G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001097642.3:c.413G>C - 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
SCV003200661Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(May 28, 2022) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Clinical and biophysical characterization of 19 GJB1 mutations.

Tsai PC, Yang DM, Liao YC, Chiu TY, Kuo HC, Su YP, Guo YC, Soong BW, Lin KP, Liu YT, Lee YC.

Ann Clin Transl Neurol. 2016 Nov;3(11):854-865.

PubMed [citation]
PMID:
27844031
PMCID:
PMC5099531

Clinical characterization and genetic analysis of Korean patients with X-linked Charcot-Marie-Tooth disease type 1.

Hong YB, Park JM, Yu JS, Yoo DH, Nam DE, Park HJ, Lee JS, Hwang SH, Chung KW, Choi BO.

J Peripher Nerv Syst. 2017 Sep;22(3):172-181. doi: 10.1111/jns.12217.

PubMed [citation]
PMID:
28448691
See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003200661.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This variant disrupts the p.Ser138 amino acid residue in GJB1. Other variant(s) that disrupt this residue have been observed in individuals with GJB1-related conditions (PMID: 21692908, 27844031, 28448691; Invitae), which suggests that this may be a clinically significant amino acid residue. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This missense change has been observed in individuals with Charcot-Marie-Tooth disease type 1X (PMID: 21692908; Invitae). 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 138 of the GJB1 protein (p.Ser138Thr).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024