NM_000441.2(SLC26A4):c.2015G>A (p.Gly672Glu) AND Rare genetic deafness

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 19, 2015
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:: RCV000036467.6

Allele description [Variation Report for NM_000441.2(SLC26A4):c.2015G>A (p.Gly672Glu)]

NM_000441.2(SLC26A4):c.2015G>A (p.Gly672Glu)

Gene:

SLC26A4:solute carrier family 26 member 4 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7q22.3

Genomic location:

Preferred name:

NM_000441.2(SLC26A4):c.2015G>A (p.Gly672Glu)

HGVS:

NC_000007.14:g.107702038G>A
NG_008489.1:g.46404G>A
NM_000441.2:c.2015G>AMANE SELECT
NP_000432.1:p.Gly672Glu
NC_000007.13:g.107342483G>A
NM_000441.1:c.2015G>A
O43511:p.Gly672Glu
c.2015G>A

Protein change:

G672E

Links:

UniProtKB: O43511#VAR_021677; dbSNP: rs111033309

NCBI 1000 Genomes Browser:

rs111033309

Molecular consequence:

NM_000441.2:c.2015G>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
SCV000060122	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Pathogenic (Feb 19, 2015)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 9618167, 11317356, 11932316, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000060122

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Pathogenic
(Feb 19, 2015)

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	not provided	4	3	not provided	not provided	not provided	clinical testing

Citations

PubMed

Molecular analysis of the PDS gene in Pendred syndrome.

Coyle B, Reardon W, Herbrick JA, Tsui LC, Gausden E, Lee J, Coffey R, Grueters A, Grossman4 A, Phelps PD, Luxon L, Kendall-Taylor P, Scherer SW, Trembath RC.

Hum Mol Genet. 1998 Jul;7(7):1105-12.

PubMed [citation]

PMID:: 9618167

Pendred syndrome, DFNB4, and PDS/SLC26A4 identification of eight novel mutations and possible genotype-phenotype correlations.

Campbell C, Cucci RA, Prasad S, Green GE, Edeal JB, Galer CE, Karniski LP, Sheffield VC, Smith RJ.

Hum Mutat. 2001 May;17(5):403-11.

PubMed [citation]

PMID:: 11317356

See all PubMed Citations (4)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000060122.6

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

Description

The p.Gly672Glu variant in SLC26A4 has been reported in 3 probands with the clin ical features of Pendred syndrome, and was identified by our laboratory in 1 ind ividual with hearing loss and EVA. The variant segregated with Pendred syndrome or hearing loss in 4 affected family members across 3 families, and all affected individuals were either homozygous for this variant or carried a second SLC26A4 variant (Coyle 1998, Campbell 2001, LMM unpublished data). In addition, functio nal analysis revealed that this variant causes the protein to be retained in the cytoplasm and abolishes its normal function at the cell surface (Taylor 2002). This variant was also identified in 5/66278 European chromosomes by the Exome Ag gregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs111033309); however, this frequency is low enough to be consistent with a recessive carrier frequency. In summary, the p.Gly672Glu variant meets our criteria to be classifi ed as pathogenic.

#	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		4	not provided	3	not provided

Last Updated: Apr 13, 2025

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