VCV000043570.50 - ClinVar

NM_000441.2(SLC26A4):c.898A>C (p.Ile300Leu)

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Benign/Likely benign
Benign (5); Likely benign (3)

8 out of 13 submissions contributed to this classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000441.2(SLC26A4):c.898A>C (p.Ile300Leu)

Variation ID: 43570 Accession: VCV000043570.50

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 7q22.3 7: 107683334 (GRCh38) [ NCBI UCSC ] 7: 107323779 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Mar 29, 2015	Apr 25, 2026	Feb 2, 2026

HGVS

Nucleotide	Protein	Molecular consequence
NM_000441.2:c.898A>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000432.1:p.Ile300Leu	missense
NC_000007.14:g.107683334A>C
NC_000007.13:g.107323779A>C
NG_008489.1:g.27700A>C

Protein change

I300L

Other names

Canonical SPDI

NC_000007.14:107683333:A:C

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

0.00479 (C)

Allele frequency Help The frequency of the allele represented by this VCV record.

1000 Genomes Project 30x 0.00578

The Genome Aggregation Database (gnomAD) 0.00450

The Genome Aggregation Database (gnomAD) 0.00423

1000 Genomes Project 0.00479

The Genome Aggregation Database (gnomAD), exomes 0.00100

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00354

Trans-Omics for Precision Medicine (TOPMed) 0.00475

Links

ClinGen: CA132740 dbSNP: rs111033304 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
SLC26A4		-	-	GRCh38 GRCh37	1640	1866

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
not specified	Benign (3)	criteria provided, multiple submitters, no conflicts	Oct 30, 2017	RCV000036511.15
Pendred syndrome	Benign/Likely benign (2)	no assertion criteria provided	Jan 1, 2020	RCV000169080.5
not provided	Benign/Likely benign (6)	criteria provided, multiple submitters, no conflicts	Feb 2, 2026	RCV000888731.38
Autosomal recessive nonsyndromic hearing loss 4 Pendred syndrome	Likely benign (1)	criteria provided, single submitter	Jan 3, 2022	RCV002496566.1
SLC26A4-related disorder	Benign (1)	no assertion criteria provided	Jul 24, 2019	RCV004541097.2

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	Expand all rows Collapse all rows Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Likely benign (Nov 14, 2018) C Contributing to aggregate classification	criteria provided, single submitter (Athena Diagnostics Criteria)	not provided	Athena Diagnostics Accession: SCV001145689.1 First in ClinVar: Jan 19, 2020 Last updated: Jan 19, 2020	Publications: PubMed (5) PubMed: 21045265‚ 21704276‚ 23280318‚ 23617710‚ 25394566 Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (Nov 15, 2018) C Contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	not provided	GeneDx Accession: SCV000730595.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018	Comment: show This variant is associated with the following publications: (PMID: 25394566, 23617710, 21045265, 23280318, 30245029) (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Benign (Feb 02, 2026) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	not provided	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001032384.8 First in ClinVar: Dec 17, 2019 Last updated: Mar 07, 2026	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (Feb 01, 2023) C Contributing to aggregate classification	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	not provided	CeGaT Center for Human Genetics Tuebingen Accession: SCV004155764.21 First in ClinVar: Nov 20, 2023 Last updated: Apr 25, 2026	Comment: show SLC26A4: BS1, BS2 (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes Number of individuals with the variant: 1

Benign (Jun 21, 2011) C Contributing to aggregate classification	criteria provided, single submitter (LMM Criteria)	not specified	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV000060166.6 First in ClinVar: May 03, 2013 Last updated: Aug 26, 2019	Comment: show Ile300Leu in exon 7 of SLC26A4: This variant is predicted to be benign because i t has been identified in 1.3% (140/10384) of African chromosomes including 3 hom ozygotes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.o rg; dbSNP rs111033304). (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: not provided more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: not provided Number of individuals with the variant: 10

Benign (Oct 30, 2017) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	not specified	Genetic Services Laboratory, University of Chicago Accession: SCV002069841.1 First in ClinVar: Jan 29, 2022 Last updated: Jan 29, 2022	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: no Observation 1 Collection method: clinical testing Allele origin: germline Affected status: no

Likely benign (-) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	not provided (Autosomal recessive inheritance)	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005228497.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024	Observation: 1 Collection method: not provided Allele origin: germline Affected status: yes Observation 1 Collection method: not provided Allele origin: germline Affected status: yes

Likely benign (Jan 03, 2022) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Pendred syndrome Autosomal recessive nonsyndromic hearing loss 4	Fulgent Genetics, Fulgent Genetics Accession: SCV002810851.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022	Observation: 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown

Likely benign (-) N Not contributing to aggregate classification	no assertion criteria provided	not provided	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ Study: VKGL Data-share Consensus Accession: SCV001954409.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Benign (-) N Not contributing to aggregate classification	no assertion criteria provided	not specified	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center Study: VKGL Data-share Consensus Accession: SCV001964619.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Benign (Jul 24, 2019) N Not contributing to aggregate classification	no assertion criteria provided	SLC26A4-related condition	PreventionGenetics, part of Exact Sciences Accession: SCV004766810.2 First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024	Comment: show This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Likely benign (Apr 26, 2014) N Not contributing to aggregate classification	no assertion criteria provided	Pendred's syndrome (Autosomal recessive inheritance)	Counsyl Accession: SCV000220252.3 First in ClinVar: Mar 29, 2015 Last updated: Jul 05, 2025	Publications: PubMed (3) PubMed: 21045265‚ 21704276‚ 23280318 Comment: show This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com. (less) Observation: 1 Collection method: literature only Allele origin: unknown Affected status: unknown Observation 1 Collection method: literature only Allele origin: unknown Affected status: unknown

Benign (Jan 01, 2020) N Not contributing to aggregate classification	no assertion criteria provided	Pendred syndrome	Natera, Inc. Accession: SCV001459862.1 First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Comment:

Ile300Leu in exon 7 of SLC26A4: This variant is predicted to be benign because i t has been identified in 1.3% (140/10384) of African chromosomes including 3 hom ozygotes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.o rg; dbSNP rs111033304).

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Evaluation of genotype-phenotype relationships in patients referred for endocrine assessment in suspected Pendred syndrome.	Soh LM	European journal of endocrinology	2015	PMID: 25394566
How far are we from understanding the genetic basis of Hashimoto's thyroiditis?	Jabrocka-Hybel A	International reviews of immunology	2013	PMID: 23617710
Screening of SLC26A4 gene in autoimmune thyroid diseases.	Kallel R	International journal of immunogenetics	2013	PMID: 23280318
Mutation analysis of SLC26A4 for Pendred syndrome and nonsyndromic hearing loss by high-resolution melting.	Chen N	The Journal of molecular diagnostics : JMD	2011	PMID: 21704276
SLC26A4 variations among Graves' hyper-functioning thyroid gland.	Hadj-Kacem H	Disease markers	2010	PMID: 21045265

Text-mined citations for rs111033304 ...

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 Apr 26, 2026