NM_000166.6(GJB1):c.37G>A (p.Val13Met) AND Charcot-Marie-Tooth Neuropathy X

Clinical significance:Likely pathogenic (Last evaluated: Feb 4, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000808363.3

Allele description [Variation Report for NM_000166.6(GJB1):c.37G>A (p.Val13Met)]

NM_000166.6(GJB1):c.37G>A (p.Val13Met)

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.37G>A (p.Val13Met)
HGVS:
  • NC_000023.11:g.71223744G>A
  • NG_008357.1:g.13533G>A
  • NM_000166.6:c.37G>AMANE SELECT
  • NM_001097642.3:c.37G>A
  • NP_000157.1:p.Val13Met
  • NP_001091111.1:p.Val13Met
  • LRG_245t2:c.37G>A
  • LRG_245:g.13533G>A
  • LRG_245p2:p.Val13Met
  • NC_000023.10:g.70443594G>A
  • NM_000166.5:c.37G>A
Protein change:
V13M
Links:
dbSNP: rs104894820
NCBI 1000 Genomes Browser:
rs104894820
Molecular consequence:
  • NM_000166.6:c.37G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001097642.3:c.37G>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
SCV000948470Invitaecriteria provided, single submitter
Likely pathogenic
(Feb 4, 2020)
germlineclinical testing

PubMed (4)
[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

[Analysis of CX32 gene mutation and related clinical features in Chinese Han Charcot-Marie-Tooth families].

Zhan YJ, Zi XH, Li L, Li XB, Huang SX, Li L, Li XG, Hu ZM, Pan Q, Xia K, Tang BS, Zhang RX.

Zhonghua Yi Xue Za Zhi. 2012 Jun 5;92(21):1463-7. Chinese.

PubMed [citation]
PMID:
22944031

New connexin32 mutations associated with X-linked Charcot-Marie-Tooth disease.

Bone LJ, Dahl N, Lensch MW, Chance PF, Kelly T, Le Guern E, Magi S, Parry G, Shapiro H, Wang S, et al.

Neurology. 1995 Oct;45(10):1863-6.

PubMed [citation]
PMID:
7477983
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV000948470.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change replaces valine with methionine at codon 13 of the GJB1 protein (p.Val13Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. This variant is present in population databases (rs104894820, ExAC 0.01%). This variant has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 22944031). ClinVar contains an entry for this variant (Variation ID: 637129). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt GJB1 protein function. This variant disrupts the p.Val13 amino acid residue in GJB1. Other variant(s) that disrupt this residue have been observed in individuals with GJB1-related conditions (PMID: 7477983, 27544631), which suggests that this may be a clinically significant amino acid residue. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

Last Updated: Nov 27, 2021

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