NM_000166.6(GJB1):c.376C>T (p.His126Tyr) AND not provided

Clinical significance:Likely pathogenic (Last evaluated: Sep 2, 2015)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000236069.1

Allele description [Variation Report for NM_000166.6(GJB1):c.376C>T (p.His126Tyr)]

NM_000166.6(GJB1):c.376C>T (p.His126Tyr)

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.376C>T (p.His126Tyr)
HGVS:
  • NC_000023.11:g.71224083C>T
  • NG_008357.1:g.13872C>T
  • NM_000166.6:c.376C>TMANE SELECT
  • NM_001097642.3:c.376C>T
  • NP_000157.1:p.His126Tyr
  • NP_001091111.1:p.His126Tyr
  • LRG_245t2:c.376C>T
  • LRG_245:g.13872C>T
  • LRG_245p2:p.His126Tyr
  • NC_000023.10:g.70443933C>T
  • NM_000166.5:c.376C>T
  • P08034:p.His126Tyr
Protein change:
H126Y
Links:
UniProtKB: P08034#VAR_029923; dbSNP: rs879253995
NCBI 1000 Genomes Browser:
rs879253995
Molecular consequence:
  • NM_000166.6:c.376C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001097642.3:c.376C>T - 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
SCV000293099GeneDxcriteria provided, single submitter
Likely pathogenic
(Sep 2, 2015)
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, SCV000293099.10

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

Description

The H126Y variant has been previously reported in a male patient with features of CMT; the variant was also identified in his mother and sister who had pes cavus, his maternal uncle with foot deformities and walking difficulty, and in a younger brother and sister who were both clinically unaffected at 10 and 8 years of age, respectively (Verhelst et al., 2000). It 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 H126Y variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Missense variants in nearby residues (V120E, K124N, V125D, I127F/S/M, S128P/L, T130I, L131P) have been reported in the Human Gene Mutation Database in association with CMTX1 (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, this variant is a strong candidate for a pathogenic variant, however the possibility that it is a benign variant cannot be excluded.

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

Last Updated: Oct 24, 2021

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