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NM_000441.2(SLC26A4):c.1975G>C (p.Val659Leu)

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Interpretation:
Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
5 (Most recent: Jan 7, 2021)
Last evaluated:
Aug 27, 2020
Accession:
VCV000188889.8
Variation ID:
188889
Description:
single nucleotide variant
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NM_000441.2(SLC26A4):c.1975G>C (p.Val659Leu)

Allele ID
186740
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
7q22.3
Genomic location
7: 107701998 (GRCh38) GRCh38 UCSC
7: 107342443 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000007.13:g.107342443G>C
NC_000007.14:g.107701998G>C
NG_008489.1:g.46364G>C
NM_000441.2:c.1975G>C MANE Select NP_000432.1:p.Val659Leu missense
Protein change
V659L
Other names
-
Canonical SPDI
NC_000007.14:107701997:G:C
Functional consequence
loss_of_function_variant [Sequence Ontology SO:0002054]
Global minor allele frequency (GMAF)
0.00020 (C)

Allele frequency
1000 Genomes Project 0.00020
The Genome Aggregation Database (gnomAD), exomes 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00001
The Genome Aggregation Database (gnomAD) 0.00006
Exome Aggregation Consortium (ExAC) 0.00001
Links
ClinGen: CA274086
dbSNP: rs200455203
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Likely pathogenic 1 criteria provided, single submitter Jul 17, 2014 RCV000169245.1
Pathogenic 3 criteria provided, single submitter Jul 1, 2017 RCV000515737.4
Pathogenic 1 criteria provided, single submitter Aug 27, 2020 RCV001048975.2

Clinical features observed in individuals with this variant

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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
SLC26A4 - - GRCh38
GRCh37
749 825

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely pathogenic
(Jul 17, 2014)
criteria provided, single submitter
Method: literature only
Pendred's syndrome
(Autosomal recessive inheritance)
Allele origin: unknown
Counsyl
Accession: SCV000220524.1
Submitted: (Mar 11, 2015)
Evidence details
Publications
PubMed (14)
Pathogenic
(Jul 01, 2017)
criteria provided, single submitter
Method: clinical testing
Deafness, autosomal recessive 4, with enlarged vestibular aqueduct
Allele origin: germline
Division of Hearing and Balance Research,National Hospital Organization Tokyo Medical Center
Accession: SCV000611821.1
Submitted: (Jul 26, 2017)
Evidence details
Pathogenic
(Aug 27, 2020)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
Invitae
Accession: SCV001213005.2
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (8)
Comment:
This sequence change replaces valine with leucine at codon 659 of the SLC26A4 protein (p.Val659Leu). The valine residue is moderately conserved and there is a … (more)
Likely pathogenic
(Feb 26, 2019)
no assertion criteria provided
Method: case-control
Deafness, autosomal recessive 4, with enlarged vestibular aqueduct
Allele origin: inherited
Genetic Testing Center for Deafness, Department of Otolaryngology Head & Neck Surgery,Institute of Otolaryngology, Chinese PLA General Hospital
Accession: SCV000902378.1
Submitted: (Apr 29, 2019)
Evidence details
Affects
(Aug 20, 2019)
no assertion criteria provided
Method: clinical testing, in vitro
Deafness, autosomal recessive 4, with enlarged vestibular aqueduct
(Autosomal recessive inheritance)
Allele origin: inherited, germline
National Institute of Sensory Organs,National Hospital Organization Tokyo Medical Center
Additional submitter:
The Hugh Knowles Center for Clinical and Basic Science in Hearing and Its Disorders,Northwestern University
Accession: SCV000994902.2
Submitted: (Oct 30, 2019)
Evidence details
Publications
PubMed (4)
Comment:
in vitro experiment

Functional evidence

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Functional consequence Method Result Submitter Supporting information
loss_of_function_variant
  1. Method not provided
  1. HCO3-/Cl- exchange_impaired; I-/Cl- exchange_impaired; signal at cell membrane_positive; intracellular puncta_positive; splicing_unaffected
National Institute of Sensory Organs,National Hospital Organization Tokyo Medical Center
Additional submitter:
The Hugh Knowles Center for Clinical and Basic Science in Hearing and Its Disorders,Northwestern University
Accession: SCV000994902.2
Submitted: (Oct 30, 2019)
Evidence details
Publications
PubMed (4)

Citations for this variant

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Title Author Journal Year Link
Systematic quantification of the anion transport function of pendrin (SLC26A4) and its disease-associated variants. Wasano K Human mutation 2020 PMID: 31599023
Mono-allelic mutations of SLC26A4 is over-presented in deaf patients with non-syndromic enlarged vestibular aqueduct. Pang X International journal of pediatric otorhinolaryngology 2015 PMID: 26100058
KCNJ10 may not be a contributor to nonsyndromic enlargement of vestibular aqueduct (NSEVA) in Chinese subjects. Zhao J PloS one 2014 PMID: 25372295
Comparative study of mutation spectrums of MT-RNR1 m.1555A>G, GJB2, and SLC26A4 between familial and sporadic patients with nonsyndromic sensorineural hearing loss in Chinese Han. Li Q Chinese medical journal 2014 PMID: 25266519
Developing regional genetic counseling for southern Chinese with nonsyndromic hearing impairment: a unique mutational spectrum. Chen K Journal of translational medicine 2014 PMID: 24612839
Mutation spectrum and genotype-phenotype correlation of hearing loss patients caused by SLC26A4 mutations in the Japanese: a large cohort study. Miyagawa M Journal of human genetics 2014 PMID: 24599119
Genetic mutations in nonsyndromic deafness patients of Chinese minority and Han ethnicities in Yunnan, China. Xin F Journal of translational medicine 2013 PMID: 24341454
Molecular etiology of hearing impairment associated with nonsyndromic enlarged vestibular aqueduct in East China. Chai Y American journal of medical genetics. Part A 2013 PMID: 23918157
Novel mutations of SLC26A4 in Chinese patients with nonsyndromic hearing loss. Yao G Acta oto-laryngologica 2013 PMID: 23638949
Compound heterozygous mutations of SLC26A4 in 4 Chinese families with enlarged vestibular aqueduct. Yao G International journal of pediatric otorhinolaryngology 2013 PMID: 23385134
Identification of SLC26A4 c.919-2A>G compound heterozygosity in hearing-impaired patients to improve genetic counseling. Li Q Journal of translational medicine 2012 PMID: 23151025
Simultaneous screening of multiple mutations by invader assay improves molecular diagnosis of hereditary hearing loss: a multicenter study. Usami S PloS one 2012 PMID: 22384008
Genetic diagnosis and cochlear implantation for patients with nonsyndromic hearing loss and enlarged vestibular aqueduct. Lai R The Journal of laryngology and otology 2012 PMID: 22289209
Extremely discrepant mutation spectrum of SLC26A4 between Chinese patients with isolated Mondini deformity and enlarged vestibular aqueduct. Huang S Journal of translational medicine 2011 PMID: 21961810
Identification of SLC26A4 mutations in patients with hearing loss and enlarged vestibular aqueduct using high-resolution melting curve analysis. Mercer S Genetic testing and molecular biomarkers 2011 PMID: 21366435
Comprehensive molecular etiology analysis of nonsyndromic hearing impairment from typical areas in China. Yuan Y Journal of translational medicine 2009 PMID: 19744334
Efficient molecular genetic diagnosis of enlarged vestibular aqueducts in East Asians. Choi BY Genetic testing and molecular biomarkers 2009 PMID: 19645628
Molecular etiology of hearing impairment in Inner Mongolia: mutations in SLC26A4 gene and relevant phenotype analysis. Dai P Journal of translational medicine 2008 PMID: 19040761
GJB2, SLC26A4 and mitochondrial DNA A1555G mutations in prelingual deafness in Northern Chinese subjects. Guo YF Acta oto-laryngologica 2008 PMID: 18274916
A distinct spectrum of SLC26A4 mutations in patients with enlarged vestibular aqueduct in China. Wang QJ Clinical genetics 2007 PMID: 17718863
Molecular analysis of hearing loss associated with enlarged vestibular aqueduct in the mainland Chinese: a unique SLC26A4 mutation spectrum. Hu H Journal of human genetics 2007 PMID: 17443271

Text-mined citations for rs200455203...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Sep 29, 2021