NM_000441.2(SLC26A4):c.2171A>G (p.Asp724Gly) AND SLC26A4-Related Disorders

Clinical significance:Likely pathogenic (Last evaluated: Dec 3, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_000441.2(SLC26A4):c.2171A>G (p.Asp724Gly)]

NM_000441.2(SLC26A4):c.2171A>G (p.Asp724Gly)

SLC26A4:solute carrier family 26 member 4 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_000441.2(SLC26A4):c.2171A>G (p.Asp724Gly)
  • NC_000007.14:g.107710135A>G
  • NG_008489.1:g.54501A>G
  • NM_000441.2:c.2171A>GMANE SELECT
  • NP_000432.1:p.Asp724Gly
  • NC_000007.13:g.107350580A>G
  • NM_000441.1:c.2171A>G
Protein change:
dbSNP: rs757820624
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_000441.2:c.2171A>G - missense variant - [Sequence Ontology: SO:0001583]


SLC26A4-Related Disorders
MedGen: CN239421

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000915194Illumina Clinical Services Laboratory,Illuminacriteria provided, single submitter
Likely pathogenic
(Dec 3, 2018)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing



Pendred syndrome and DFNB4-mutation screening of SLC26A4 by denaturing high-performance liquid chromatography and the identification of eleven novel mutations.

Prasad S, Kölln KA, Cucci RA, Trembath RC, Van Camp G, Smith RJ.

Am J Med Genet A. 2004 Jan 1;124A(1):1-9.

PubMed [citation]

Functional assessment of allelic variants in the SLC26A4 gene involved in Pendred syndrome and nonsyndromic EVA.

Pera A, Dossena S, Rodighiero S, Gandía M, Bottà G, Meyer G, Moreno F, Nofziger C, Hernández-Chico C, Paulmichl M.

Proc Natl Acad Sci U S A. 2008 Nov 25;105(47):18608-13. doi: 10.1073/pnas.0805831105. Epub 2008 Nov 18.

PubMed [citation]
See all PubMed Citations (3)

Details of each submission

From Illumina Clinical Services Laboratory,Illumina, SCV000915194.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)


The SLC26A4 c.2171A>G (p.Asp724Gly) missense variant has been reported in at least three studies and is found in a total of four probands, including three probands in a compound heterozygous state and one proband in a heterozygous state (Prasad et al. 2004; Pera et al. 2008; Ladsous et al. 2014). Of the three compound heterozygous probands; two probands were clinically diagnosed with Pendred syndrome and one proband was noted to have non-syndromic enlarged vestibular aqueduct. The heterozygous proband was described to have non-syndromic hearing loss, although an alternate etiology was suspected to be causative, this phenotype and thus this proband was considered a coincidental carrier of the p.Asp724Gly variant (Pera et al. 2008). The p.Asp724Gly variant was reported in two of 648 controls alleles and is reported at a frequency of 0.000032 in the European (non-Finnish) population of the Genome Aggregation Database. The Asp724 residue is highly conserved. The p.Asp724Gly variant protein was expressed in HEK-293 phoenix cells and had no detectable iodide transport when analyzed with fluorometry, indicating complete inactivation in comparison to wildtype (Pera et al. 2008). Based on the evidence, the p.Asp724Gly variant is classified as likely pathogenic for SLC26A4-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 23, 2021

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