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NM_000166.6(GJB1):c.2T>A (p.Met1Lys) AND Charcot-Marie-Tooth Neuropathy X

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jul 14, 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:
RCV001220843.8

Allele description [Variation Report for NM_000166.6(GJB1):c.2T>A (p.Met1Lys)]

NM_000166.6(GJB1):c.2T>A (p.Met1Lys)

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.2T>A (p.Met1Lys)
HGVS:
  • NC_000023.11:g.71223709T>A
  • NG_008357.1:g.13498T>A
  • NM_000166.6:c.2T>AMANE SELECT
  • NM_001097642.3:c.2T>A
  • NP_000157.1:p.Met1Lys
  • NP_001091111.1:p.Met1Lys
  • LRG_245t2:c.2T>A
  • LRG_245:g.13498T>A
  • LRG_245p2:p.Met1Lys
  • NC_000023.10:g.70443559T>A
  • NM_000166.5:c.2T>A
Protein change:
M1K
Links:
dbSNP: rs1602348519
NCBI 1000 Genomes Browser:
rs1602348519
Molecular consequence:
  • NM_000166.6:c.2T>A - initiator_codon_variant - [Sequence Ontology: SO:0001582]
  • NM_001097642.3:c.2T>A - initiator_codon_variant - [Sequence Ontology: SO:0001582]
  • NM_000166.6:c.2T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001097642.3:c.2T>A - 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

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001392855Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Jul 14, 2023)
germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Six new gap junction beta 1 gene mutations and their phenotypic expression in Czech patients with Charcot-Marie-Tooth disease.

Brozková D, Mazanec R, Haberlová J, Sakmaryová I, Subrt I, Seeman P.

Genet Test Mol Biomarkers. 2010 Feb;14(1):3-7. doi: 10.1089/gtmb.2009.0093.

PubMed [citation]
PMID:
20039784

Whole-exome sequencing in patients with inherited neuropathies: outcome and challenges.

Schabhüttl M, Wieland T, Senderek J, Baets J, Timmerman V, De Jonghe P, Reilly MM, Stieglbauer K, Laich E, Windhager R, Erwa W, Trajanoski S, Strom TM, Auer-Grumbach M.

J Neurol. 2014 May;261(5):970-82. doi: 10.1007/s00415-014-7289-8. Epub 2014 Mar 15.

PubMed [citation]
PMID:
24627108
See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001392855.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. This sequence change affects the initiator methionine of the GJB1 mRNA. The next in-frame methionine is located at codon 34. This variant is not present in population databases (gnomAD no frequency). Disruption of the initiator codon has been observed in individuals with GJB1-related conditions (PMID: 20039784, 24627108, 24958582, 25771809; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 949392). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that disruption of the initiator codon affects GJB1 function (PMID: 25771809).

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

Last Updated: Sep 29, 2024