NM_000166.6(GJB1):c.205T>C (p.Phe69Leu) AND Charcot-Marie-Tooth Neuropathy X

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 7, 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:: RCV002536914.3

Allele description [Variation Report for NM_000166.6(GJB1):c.205T>C (p.Phe69Leu)]

NM_000166.6(GJB1):c.205T>C (p.Phe69Leu)

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.205T>C (p.Phe69Leu)

HGVS:

NC_000023.11:g.71223912T>C
NG_008357.1:g.13701T>C
NM_000166.6:c.205T>CMANE SELECT
NM_001097642.3:c.205T>C
NP_000157.1:p.Phe69Leu
NP_001091111.1:p.Phe69Leu
LRG_245t2:c.205T>C
LRG_245:g.13701T>C
LRG_245p2:p.Phe69Leu
NC_000023.10:g.70443762T>C
NM_000166.5:c.205T>C

Protein change:

F69L

Links:

dbSNP: rs1602348917

NCBI 1000 Genomes Browser:

rs1602348917

Molecular consequence:

NM_000166.6:c.205T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001097642.3:c.205T>C - 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
SCV003445254	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 7, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 10923043, 17100997, 29998508, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003445254

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 7, 2022)

germline

clinical testing

PubMed (4)
[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

Mutations in the peripheral myelin protein zero and connexin32 genes detected by non-isotopic RNase cleavage assay and their phenotypes in Japanese patients with Charcot-Marie-Tooth disease.

Yoshihara T, Yamamoto M, Doyu M, Mis KI, Hattori N, Hasegawa Y, Mokuno K, Mitsuma T, Sobue G.

Hum Mutat. 2000 Aug;16(2):177-8.

PubMed [citation]

PMID:: 10923043

Clinical and molecular analysis of X-linked Charcot-Marie-Tooth disease type 1 in Spanish population.

Casasnovas C, Banchs I, Corral J, Martínez-Matos JA, Volpini V.

Clin Genet. 2006 Dec;70(6):516-23. Erratum in: Clin Genet. 2007 Feb;71(2):194. Clin Genet. 2008 Feb;73(2):196.

PubMed [citation]

PMID:: 17100997

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003445254.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This variant is not present in population databases (gnomAD no frequency). 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: 637244). This missense change has been observed in individuals with Charcot-Marie-Tooth disease (PMID: 10923043, 17100997, 29998508). It has also been observed to segregate with disease in related individuals. This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 69 of the GJB1 protein (p.Phe69Leu).

#	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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