NM_004004.6(GJB2):c.548C>T (p.Ser183Phe) AND not provided

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Nov 15, 2023
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:: RCV003127129.2

Allele description [Variation Report for NM_004004.6(GJB2):c.548C>T (p.Ser183Phe)]

NM_004004.6(GJB2):c.548C>T (p.Ser183Phe)

Gene:

GJB2:gap junction protein beta 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

13q12.11

Genomic location:

Preferred name:

NM_004004.6(GJB2):c.548C>T (p.Ser183Phe)

HGVS:

NC_000013.11:g.20189034G>A
NG_008358.1:g.8942C>T
NM_004004.6:c.548C>TMANE SELECT
NP_003995.2:p.Ser183Phe
LRG_1350t1:c.548C>T
LRG_1350:g.8942C>T
LRG_1350p1:p.Ser183Phe
NC_000013.10:g.20763173G>A
NM_004004.5:c.548C>T

Protein change:

S183F

Molecular consequence:

NM_004004.6:c.548C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003803510	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely pathogenic (Nov 15, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003803510

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely pathogenic
(Nov 15, 2023)

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	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From GeneDx, SCV003803510.2

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

Description

Identified in a parent and child with palmoplantar keratoderma and sensorineural hearing loss in published literature (PMID: 18787097); Published functional studies demonstrate a dominant negative effect due to the formation of non-functional gap junctions with wild-type connexin 26, as well as a gain-of-function effect due to the ability to intermix with connexin 30 and connexin 43 (PMID: 28428247, 26763442, 32300592); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 33466560, 24975403, 18787097, 26763442, 28428247, 21933662, 32300592, 22547955, 21484990, 25388846, 35938034)

#	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

Last Updated: Oct 8, 2024

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