NM_000441.2(SLC26A4):c.412G>C (p.Val138Leu) AND Autosomal recessive nonsyndromic hearing loss 4

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: May 31, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV003152725.4

Allele description [Variation Report for NM_000441.2(SLC26A4):c.412G>C (p.Val138Leu)]

NM_000441.2(SLC26A4):c.412G>C (p.Val138Leu)

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.412G>C (p.Val138Leu)

HGVS:

NC_000007.14:g.107672245G>C
NG_008489.1:g.16611G>C
NM_000441.2:c.412G>CMANE SELECT
NP_000432.1:p.Val138Leu
NC_000007.13:g.107312690G>C
NM_000441.1:c.412G>C

Protein change:

V138L

Links:

dbSNP: rs111033199

NCBI 1000 Genomes Browser:

rs111033199

Molecular consequence:

NM_000441.2:c.412G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Autosomal recessive nonsyndromic hearing loss 4 (DFNB4)
Synonyms:: NEUROSENSORY NONSYNDROMIC RECESSIVE DEAFNESS 4; DEAFNESS, AUTOSOMAL RECESSIVE 4, WITH ENLARGED VESTIBULAR AQUEDUCT, DIGENIC; Nonsyndromic enlarged vestibular aqueduct (NSEVA); See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010933; MedGen: C3538946; Orphanet: 90636; OMIM: 600791

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003841669	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 23, 2023)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 19645628, 25741868
SCV004201923	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (May 31, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003841669

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Feb 23, 2023)

unknown

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV004201923

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(May 31, 2023)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Efficient molecular genetic diagnosis of enlarged vestibular aqueducts in East Asians.

Choi BY, Stewart AK, Nishimura KK, Cha WJ, Seong MW, Park SS, Kim SW, Chun YS, Chung JW, Park SN, Chang SO, Kim CS, Alper SL, Griffith AJ, Oh SH.

Genet Test Mol Biomarkers. 2009 Oct;13(5):679-87. doi: 10.1089/gtmb.2009.0054.

PubMed [citation]

PMID:: 19645628
PMCID:: PMC2953255

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From 3billion, SCV003841669.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

The variant is not observed in the gnomAD v2.1.1 dataset. Functional studies provide moderate evidence of the variant having a damaging effect on the gene or gene product (PMID: 19645628). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.82; 3Cnet: 0.60). Same nucleotide change resulting in same amino acid change (ClinVar ID: VCV000556058) and a different missense change at the same codon (p.Val138Phe / ClinVar ID: VCV000004835) have been previously reported as pathogenic/likely pathogenic with strong evidence. Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Baylor Genetics, SCV004201923.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 20, 2025

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