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NM_000441.1(SLC26A4):c.349C>T

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Interpretation:
Likely pathogenic​

Review status:
reviewed by expert panel FDA Recognized Database
Submissions:
8 (Most recent: May 27, 2021)
Last evaluated:
Sep 26, 2018
Accession:
VCV000043555.9
Variation ID:
43555
Description:
single nucleotide variant
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NM_000441.2(SLC26A4):c.349C>T (p.Leu117Phe)

Allele ID
52724
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
7q22.3
Genomic location
7: 107672182 (GRCh38) GRCh38 UCSC
7: 107312627 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000007.13:g.107312627C>T
NC_000007.14:g.107672182C>T
NM_000441.2:c.349C>T MANE Select NP_000432.1:p.Leu117Phe missense
... more HGVS
Protein change
L117F
Other names
NM_000441.1(SLC26A4):c.349C>T(p.Leu117Phe)
NM_000441.1(SLC26A4):c.349C>T
Canonical SPDI
NC_000007.14:107672181:C:T
Functional consequence
functionally_normal [Sequence Ontology SO:0002219]
Global minor allele frequency (GMAF)
0.00020 (T)

Allele frequency
Trans-Omics for Precision Medicine (TOPMed) 0.00012
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00015
Exome Aggregation Consortium (ExAC) 0.00023
The Genome Aggregation Database (gnomAD), exomes 0.00033
1000 Genomes Project 0.00020
The Genome Aggregation Database (gnomAD) 0.00003
Links
ClinGen: CA132727
UniProtKB: O43511#VAR_021647
dbSNP: rs145254330
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Likely pathogenic 3 reviewed by expert panel Sep 26, 2018 RCV000225040.2
Likely pathogenic 1 criteria provided, single submitter Jul 8, 2020 RCV000036491.4
Uncertain significance 3 criteria provided, single submitter Apr 27, 2017 RCV000225082.3
Uncertain significance 1 criteria provided, single submitter Nov 7, 2018 RCV000757776.2
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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
730 806

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely pathogenic
(Sep 26, 2018)
reviewed by expert panel
Method: curation
Pendred syndrome
(Autosomal recessive inheritance)
Allele origin: germline
ClinGen Hearing Loss Variant Curation Expert Panel
FDA Recognized Database
Accession: SCV000840507.4
Submitted: (Jul 18, 2019)
Evidence details
Publications
PubMed (5)
Other databases
https://erepo.clinicalgenome.org…
Comment:
This variant has been detected in 4 patients with hearing loss in trans with p.Val570Ile, p.Thr416Pro, c.-4+1>C and p.Thr193Ile (PM3_VeryStrong; Partners LMM unpublished internal data, … (more)
Uncertain significance
(Nov 07, 2018)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories
Accession: SCV000886130.2
Submitted: (Aug 05, 2019)
Evidence details
Comment:
The p.Leu117Phe variant (rs145254330) has been reported in multiple individuals with non-syndromic hearing loss (Reardon 2000, Albert 2006, Sloan-Heggen 2016); however, it has never been … (more)
Uncertain significance
(Apr 27, 2017)
criteria provided, single submitter
Method: clinical testing
Deafness, autosomal recessive 4, with enlarged vestibular aqueduct
Allele origin: germline
Illumina Clinical Services Laboratory,Illumina
Accession: SCV001321397.1
Submitted: (Feb 20, 2020)
Evidence details
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
Uncertain significance
(Apr 27, 2017)
criteria provided, single submitter
Method: clinical testing
Pendred syndrome
Allele origin: germline
Illumina Clinical Services Laboratory,Illumina
Accession: SCV001321398.1
Submitted: (Feb 20, 2020)
Evidence details
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
Likely pathogenic
(Jul 08, 2020)
criteria provided, single submitter
Method: clinical testing
Rare genetic deafness
(Autosomal recessive inheritance)
Allele origin: germline
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine
Accession: SCV000060146.7
Submitted: (May 27, 2021)
Evidence details
Publications
PubMed (7)
Comment:
The p.Leu117Phe variant in SLC26A4 has been previously reported in 8 individuals with hearing loss, 6 of whom had enlarged vestibular aqueducts, and 5 of … (more)
Pathogenic
(Feb 19, 2016)
no assertion criteria provided
Method: research
Pendred syndrome
Allele origin: germline
Laboratory of Prof. Karen Avraham,Tel Aviv University
Accession: SCV000282016.1
Submitted: (May 03, 2016)
Comment:
NSHL; recessive or Pendred, DFNB4; in one family, it might not be clear if it is syndromic of non-syndromic
Evidence details
Comment:
Congenital, profound HL
Pathogenic
(Feb 19, 2016)
no assertion criteria provided
Method: research
Enlarged vestibular aqueduct syndrome
Allele origin: germline
Laboratory of Prof. Karen Avraham,Tel Aviv University
Accession: SCV000282017.1
Submitted: (May 03, 2016)
Comment:
NSHL; recessive or Pendred, DFNB4
Evidence details
Comment:
Congenital, profound HL
other
(Aug 20, 2019)
no assertion criteria provided
Method: literature only, in vitro
Deafness, autosomal recessive 4, with enlarged vestibular aqueduct
(Autosomal recessive inheritance)
Allele origin: 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: SCV000994863.2
Submitted: (Oct 30, 2019)
Evidence details
Publications
PubMed (7)
Comment:
Benign effect in vitro experiment

Functional evidence

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Functional consequence Method Result Submitter Supporting information
functionally_normal
  1. Method not provided
  1. HCO3-/Cl- exchange_normal; I-/Cl- exchange_normal; 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: SCV000994863.2
Submitted: (Oct 30, 2019)
Evidence details
Publications
PubMed (7)

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
Genomic Landscape and Mutational Signatures of Deafness-Associated Genes. Azaiez H American journal of human genetics 2018 PMID: 30245029
Mapping pathogenic mutations suggests an innovative structural model for the pendrin (SLC26A4) transmembrane domain. Bassot C Biochimie 2017 PMID: 27771369
Comprehensive genetic testing in the clinical evaluation of 1119 patients with hearing loss. Sloan-Heggen CM Human genetics 2016 PMID: 26969326
Utilizing ethnic-specific differences in minor allele frequency to recategorize reported pathogenic deafness variants. Shearer AE American journal of human genetics 2014 PMID: 25262649
Simultaneous multigene mutation detection in patients with sensorineural hearing loss through a novel diagnostic microarray: a new approach for newborn screening follow-up. Gardner P Pediatrics 2006 PMID: 16950989
SLC26A4 gene is frequently involved in nonsyndromic hearing impairment with enlarged vestibular aqueduct in Caucasian populations. Albert S European journal of human genetics : EJHG 2006 PMID: 16570074
Distribution and frequencies of PDS (SLC26A4) mutations in Pendred syndrome and nonsyndromic hearing loss associated with enlarged vestibular aqueduct: a unique spectrum of mutations in Japanese. Tsukamoto K European journal of human genetics : EJHG 2003 PMID: 14508505
Mutations of the PDS gene, encoding pendrin, are associated with protein mislocalization and loss of iodide efflux: implications for thyroid dysfunction in Pendred syndrome. Taylor JP The Journal of clinical endocrinology and metabolism 2002 PMID: 11932316
Enlarged vestibular aqueduct: a radiological marker of pendred syndrome, and mutation of the PDS gene. Reardon W QJM : monthly journal of the Association of Physicians 2000 PMID: 10700480
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/67c2f97e-385f-494a-b06e-701135ace536 - - - -

Text-mined citations for rs145254330...

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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 Aug 27, 2021