NM_004004.6(GJB2):c.224G>A (p.Arg75Gln) AND Rare genetic deafness

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 28, 2013
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:: RCV000211764.12

Allele description [Variation Report for NM_004004.6(GJB2):c.224G>A (p.Arg75Gln)]

NM_004004.6(GJB2):c.224G>A (p.Arg75Gln)

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.224G>A (p.Arg75Gln)

HGVS:

NC_000013.11:g.20189358C>T
NG_008358.1:g.8618G>A
NM_004004.6:c.224G>AMANE SELECT
NP_003995.2:p.Arg75Gln
NP_003995.2:p.Arg75Gln
LRG_1350t1:c.224G>A
LRG_1350:g.8618G>A
LRG_1350p1:p.Arg75Gln
NC_000013.10:g.20763497C>T
NM_004004.5:c.224G>A
P29033:p.Arg75Gln

Protein change:

R75Q; ARG75GLN

Links:

UniProtKB: P29033#VAR_015936; OMIM: 121011.0026; dbSNP: rs28931593

NCBI 1000 Genomes Browser:

rs28931593

Molecular consequence:

NM_004004.6:c.224G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Rare genetic deafness
Identifiers:: MedGen: C5680250; Orphanet: 96210

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000198162	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Pathogenic (Aug 28, 2013)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 12372058, 15996214, 23451214, 20096356, 21040787, 16059934, 15790391, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000198162

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Pathogenic
(Aug 28, 2013)

germline

clinical testing

PubMed (8)
[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	not provided	2	2	not provided	not provided	not provided	clinical testing

Citations

PubMed

The novel R75Q mutation in the GJB2 gene causes autosomal dominant hearing loss and palmoplantar keratoderma in a Turkish family.

Uyguner O, Tukel T, Baykal C, Eris H, Emiroglu M, Hafiz G, Ghanbari A, Baserer N, Yuksel-Apak M, Wollnik B.

Clin Genet. 2002 Oct;62(4):306-9.

PubMed [citation]

PMID:: 12372058

Functional analysis of R75Q mutation in the gene coding for Connexin 26 identified in a family with nonsyndromic hearing loss.

Piazza V, Beltramello M, Menniti M, Colao E, Malatesta P, Argento R, Chiarella G, Gallo LV, Catalano M, Perrotti N, Mammano F, Cassandro E.

Clin Genet. 2005 Aug;68(2):161-6.

PubMed [citation]

PMID:: 15996214

See all PubMed Citations (8)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000198162.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	PubMed (8)

Description

The Arg75Gln variant in GJB2 has been identified in several individuals with hea ring loss with or without palmoplantar keratoderma, was found to segregate with disease in over 10 affected relatives, and was determined to have occurred de no vo in at least one individual (Uyguner 2002, Feldmann 2005, Posukh 2005, Piazza 2005, Wu 2011). This variant has not been identified in large population studies . In vitro functional studies indicate the Arg75Gln variant may impact protein f unction and acts in a dominant-negative manner (Piazza 2005, Yum 2010, Zhang 201 1). In summary, this variant meets our criteria to be classified as pathogenic ( http://pcpgm.partners.org/LMM).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		2	not provided	2	not provided

Last Updated: Nov 24, 2024

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