NM_000166.6(GJB1):c.372G>C (p.Lys124Asn) AND not provided

Clinical significance:Likely pathogenic (Last evaluated: Jun 23, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000216227.1

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)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000279581GeneDxcriteria provided, single submitter
Likely pathogenic
(Jun 23, 2017)
germlineclinical testing

Citation Link

Summary from all submissions

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

Details of each submission

From GeneDx, SCV000279581.9

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The K124N variant in the GJB1 gene has been reported previously in association with X-linked Charcot-Marie-Tooth disease (CMTX) (Bone et al., 1997). The K124N variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The K124N variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position where amino acids with similar properties to Lysine are tolerated across species and is predicted to be within the intracellular loop between the second and third transmembrane regions of the GJB1 protein (Bone et al., 1997; Kleopa et al., 2012). Multiple missense variants in nearby residues have been reported in the Human Gene Mutation Database in association with GJB1-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein. In silico analysis predicts this variant is probably damaging to the protein structure/function. This variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.

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

Last Updated: Nov 27, 2021

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