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NM_000166.6(GJB1):c.299A>T (p.His100Leu) AND Charcot-Marie-Tooth Neuropathy X

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Aug 6, 2020
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:
RCV001303696.8

Allele description [Variation Report for NM_000166.6(GJB1):c.299A>T (p.His100Leu)]

NM_000166.6(GJB1):c.299A>T (p.His100Leu)

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.299A>T (p.His100Leu)
HGVS:
  • NC_000023.11:g.71224006A>T
  • NG_008357.1:g.13795A>T
  • NM_000166.6:c.299A>TMANE SELECT
  • NM_001097642.3:c.299A>T
  • NP_000157.1:p.His100Leu
  • NP_001091111.1:p.His100Leu
  • LRG_245t2:c.299A>T
  • LRG_245:g.13795A>T
  • LRG_245p2:p.His100Leu
  • NC_000023.10:g.70443856A>T
  • NM_000166.5:c.299A>T
Protein change:
H100L
Links:
dbSNP: rs1602349133
NCBI 1000 Genomes Browser:
rs1602349133
Molecular consequence:
  • NM_000166.6:c.299A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001097642.3:c.299A>T - 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
SCV001492949Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Aug 6, 2020) 		germlineclinical testing

PubMed (3)
[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

Mutation in connexin 32 causes Charcot-Marie-Tooth disease in a large Chinese family.

Guo F, Shi Y, Lin Y, Liu X, Liu B, Liu Y, Yang Y, Lu F, Ma S, Yang Z.

Muscle Nerve. 2010 Nov;42(5):715-21. doi: 10.1002/mus.21756.

PubMed [citation]
PMID:
20730878

Mutation analysis in Charcot-Marie-Tooth disease type 1 (CMT1).

Sorour E, Upadhyaya M.

Hum Mutat. 1998;Suppl 1:S242-7. No abstract available.

PubMed [citation]
PMID:
9452099
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001492949.5

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

Description

This variant has not been reported in the literature in individuals with GJB1-related conditions. 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. This variant disrupts the p.His100 amino acid residue in GJB1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 20730878, 9452099). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant is not present in population databases (ExAC no frequency). This sequence change replaces histidine with leucine at codon 100 of the GJB1 protein (p.His100Leu). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and leucine.

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

Last Updated: Sep 29, 2024