NM_004004.6(GJB2):c.133G>A (p.Gly45Arg) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 25, 2018
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:: RCV000825343.4

Allele description [Variation Report for NM_004004.6(GJB2):c.133G>A (p.Gly45Arg)]

NM_004004.6(GJB2):c.133G>A (p.Gly45Arg)

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.133G>A (p.Gly45Arg)

HGVS:

NC_000013.11:g.20189449C>T
NG_008358.1:g.8527G>A
NM_004004.6:c.133G>AMANE SELECT
NP_003995.2:p.Gly45Arg
LRG_1350t1:c.133G>A
LRG_1350:g.8527G>A
LRG_1350p1:p.Gly45Arg
NC_000013.10:g.20763588C>T
NM_004004.5:c.133G>A
p.Gly45Arg

Protein change:

G45R

Links:

dbSNP: rs1326514987

NCBI 1000 Genomes Browser:

rs1326514987

Molecular consequence:

NM_004004.6:c.133G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000966638	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Uncertain significance (Jul 25, 2018)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 27761313, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000966638

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Uncertain significance
(Jul 25, 2018)

germline

clinical testing

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

Citations

PubMed

Comparative functional characterization of novel non-syndromic GJB2 gene variant p.Gly45Arg and lethal syndromic variant p.Gly45Glu.

Rodriguez-Paris J, Waldhaus J, Gordhandas JA, Pique L, Schrijver I.

PeerJ. 2016;4:e2494. doi: 10.7717/peerj.2494.

PubMed [citation]

PMID:: 27761313
PMCID:: PMC5068369

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]

PMID:: 24033266
PMCID:: PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000966638.1

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

Description

Variant classified as Uncertain Significance - Favor Pathogenic. The p.Gly45Arg variant in GJB2 has been reported in 1 individual with non-syndromic hearing los s (Rodriguez-Paris 2016). In addition, in vitro fluorescence microscopy studies suggest impaired permeability of IP3 through the connexin-26 (GJB2) channel for the p.Gly45Arg variant, potentially in an autosomal dominant manner (Rodriguez-P aris 2016). This variant has also been identified in 1/8722 of African chromosom es by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org) . Computational prediction tools and conservation analysis suggest that the p.Gl y45Arg variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, while there is some suspicion fo r a pathogenic role, the clinical significance of the p.Gly45Arg variant is unce rtain. ACMG/AMP Criteria applied: PM2; PP3; PS3_Supporting.

#	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	1	not provided

Last Updated: Oct 8, 2024

ClinVar

Relating variation to medicine