NM_000166.6(GJB1):c.208C>G (p.Pro70Ala) AND Charcot-Marie-Tooth Neuropathy X

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 24, 2022
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:: RCV000231475.8

Allele description [Variation Report for NM_000166.6(GJB1):c.208C>G (p.Pro70Ala)]

NM_000166.6(GJB1):c.208C>G (p.Pro70Ala)

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.208C>G (p.Pro70Ala)

HGVS:

NC_000023.11:g.71223915C>G
NG_008357.1:g.13704C>G
NM_000166.6:c.208C>GMANE SELECT
NM_001097642.3:c.208C>G
NP_000157.1:p.Pro70Ala
NP_001091111.1:p.Pro70Ala
LRG_245t2:c.208C>G
LRG_245:g.13704C>G
LRG_245p2:p.Pro70Ala
NC_000023.10:g.70443765C>G
NM_000166.5:c.208C>G
P08034:p.Pro70Ala

Protein change:

P70A

Links:

UniProtKB: P08034#VAR_029914; dbSNP: rs878853697

NCBI 1000 Genomes Browser:

rs878853697

Molecular consequence:

NM_000166.6:c.208C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001097642.3:c.208C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Charcot-Marie-Tooth Neuropathy X
Identifiers:: MedGen: CN118851

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000283686	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 24, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 10873293, 21692908, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000283686

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 24, 2022)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

X-linked Charcot-Marie-Tooth disease and connexin32.

Ionasescu VV.

Cell Biol Int. 1998 Nov;22(11-12):807-13.

PubMed [citation]

PMID:: 10873293

Phenotype expression in women with CMT1X.

Siskind CE, Murphy SM, Ovens R, Polke J, Reilly MM, Shy ME.

J Peripher Nerv Syst. 2011 Jun;16(2):102-7. doi: 10.1111/j.1529-8027.2011.00332.x.

PubMed [citation]

PMID:: 21692908

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000283686.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. 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: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 237122). This missense change has been observed in individuals with Charcot-Marie-Tooth disease type 1X (CMT1X) (PMID: 10873293, 21692908; Invitae). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 70 of the GJB1 protein (p.Pro70Ala).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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