NM_000166.6(GJB1):c.372G>C (p.Lys124Asn) AND Charcot-Marie-Tooth Neuropathy X

Clinical significance:Uncertain significance (Last evaluated: Sep 24, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001294422.1

Allele description [Variation Report for NM_000166.6(GJB1):c.372G>C (p.Lys124Asn)]

NM_000166.6(GJB1):c.372G>C (p.Lys124Asn)

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.372G>C (p.Lys124Asn)
HGVS:
  • NC_000023.11:g.71224079G>C
  • NG_008357.1:g.13868G>C
  • NM_000166.6:c.372G>CMANE SELECT
  • NM_001097642.3:c.372G>C
  • NP_000157.1:p.Lys124Asn
  • NP_001091111.1:p.Lys124Asn
  • LRG_245t2:c.372G>C
  • LRG_245:g.13868G>C
  • LRG_245p2:p.Lys124Asn
  • NC_000023.10:g.70443929G>C
  • NM_000166.5:c.372G>C
  • P08034:p.Lys124Asn
Protein change:
K124N
Links:
UniProtKB: P08034#VAR_002078; dbSNP: rs876661119
NCBI 1000 Genomes Browser:
rs876661119
Molecular consequence:
  • NM_000166.6:c.372G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001097642.3:c.372G>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

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001483300Invitaecriteria provided, single submitter
Uncertain significance
(Sep 24, 2020)
germlineclinical testing

PubMed (3)
[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

Connexin32 and X-linked Charcot-Marie-Tooth disease.

Bone LJ, DeschĂȘnes SM, Balice-Gordon RJ, Fischbeck KH, Scherer SS.

Neurobiol Dis. 1997;4(3-4):221-30. Review.

PubMed [citation]
PMID:
9361298

Improved diagnostic yield of neuromuscular disorders applying clinical exome sequencing in patients arising from a consanguineous population.

Fattahi Z, Kalhor Z, Fadaee M, Vazehan R, Parsimehr E, Abolhassani A, Beheshtian M, Zamani G, Nafissi S, Nilipour Y, Akbari MR, Kahrizi K, Kariminejad A, Najmabadi H.

Clin Genet. 2017 Mar;91(3):386-402. doi: 10.1111/cge.12810. Epub 2016 Jul 21.

PubMed [citation]
PMID:
27234031
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001483300.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change replaces lysine with asparagine at codon 124 of the GJB1 protein (p.Lys124Asn). The lysine residue is highly conserved and there is a moderate physicochemical difference between lysine and asparagine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of Charcot-Marie-Tooth disease (PMID: 9361298, Invitae). ClinVar contains an entry for this variant (Variation ID: 234611). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Benign; Align-GVGD: Class C). This variant disrupts the p.Lys124 amino acid residue in GJB1. Other variant(s) that disrupt this residue have been observed in individuals with GJB1-related conditions (PMID: 27234031), which suggests that this may be a clinically significant amino acid residue. 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. 6

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

Last Updated: Oct 30, 2021

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