NM_000166.6(GJB1):c.-103C>T AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Oct 30, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001570001.23

Allele description [Variation Report for NM_000166.6(GJB1):c.-103C>T]

NM_000166.6(GJB1):c.-103C>T

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.-103C>T

HGVS:

NC_000023.11:g.71223249C>T
NG_008357.1:g.13038C>T
NM_000166.6:c.-103C>TMANE SELECT
NM_001097642.3:c.-16-443C>T
LRG_245t2:c.-103C>T
LRG_245:g.13038C>T
NC_000023.10:g.70443099C>T
NM_000166.5:c.-103C>T

Links:

dbSNP: rs863224971

NCBI 1000 Genomes Browser:

rs863224971

Molecular consequence:

NM_000166.6:c.-103C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001097642.3:c.-16-443C>T - intron variant - [Sequence Ontology: SO:0001627]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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Homo sapiens serpin family E member 2 (SERPINE2), transcript variant 2, mRNA
Homo sapiens serpin family E member 2 (SERPINE2), transcript variant 2, mRNA
gi|211904151|ref|NM_001136528.1|

Nucleotide
Homo sapiens serpin family E member 2 (SERPINE2), transcript variant 1, mRNA
Homo sapiens serpin family E member 2 (SERPINE2), transcript variant 1, mRNA
gi|1890266968|ref|NM_006216.4|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000255686	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Pathogenic (Oct 6, 2021)	unknown	clinical testing	PubMed (10) [See all records that cite these PMIDs] 8757034, 10931843, 19335535, 34089394, 23827825, 28768847, 28283593, 31211173, 33136338, 26467025
SCV001794187	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Oct 30, 2023)	germline	clinical testing	Citation Link,
SCV002498150	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Mar 1, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000255686

Athena Diagnostics

criteria provided, single submitter

(Athena Diagnostics Criteria)

Pathogenic
(Oct 6, 2021)

unknown

clinical testing

PubMed (10)
[See all records that cite these PMIDs]

SCV001794187

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Oct 30, 2023)

germline

clinical testing

Citation Link,

SCV002498150

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Pathogenic
(Mar 1, 2022)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations of the noncoding region of the connexin32 gene in X-linked dominant Charcot-Marie-Tooth neuropathy.

Ionasescu VV, Searby C, Ionasescu R, Neuhaus IM, Werner R.

Neurology. 1996 Aug;47(2):541-4.

PubMed [citation]

PMID:: 8757034

Analysis of a Charcot-Marie-Tooth disease mutation reveals an essential internal ribosome entry site element in the connexin-32 gene.

Hudder A, Werner R.

J Biol Chem. 2000 Nov 3;275(44):34586-91.

PubMed [citation]

PMID:: 10931843

See all PubMed Citations (10)

Details of each submission

From Athena Diagnostics, SCV000255686.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (10)

Description

This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). This variant has been identified in multiple unrelated individuals with clinical features associated with this gene. In some published literature, this variant is referred to as c.-458C>T or c.-459C>T. This variant segregates with disease in multiple families. Assessment of experimental evidence suggests this variant results in abnormal protein function. This variant significantly affects translation by disrupting an Internal Ribosome Entry Site (IRES) (PMID: 10931843, 23827825, 34089394).

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

From GeneDx, SCV001794187.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Published functional studies indicate impaired protein expression (PMID: 10931843, 23827825); No data available from ethnically-matched control populations to assess the frequency of this variant; Also known as c.-459 C>T; This variant is associated with the following publications: (PMID: 31211173, 28283593, 23827825, 8757034, 31827005, 33136338, 34089394, 19335535, 26392352, 10931843)

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

From CeGaT Center for Human Genetics Tuebingen, SCV002498150.17

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	not provided

Description

GJB1: PP1:Strong, PM2, PS4:Moderate, PP4, PS3:Supporting

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

Last Updated: Oct 8, 2024

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