VCV000226902.40 - ClinVar

NM_001292063.2(OTOG):c.6074C>T (p.Ala2025Val)

Germline

Classification

criteria provided, conflicting classifications. Learn more about how ClinVar calculates review status.

Conflicting classifications of pathogenicity
Uncertain significance(3); Benign(1); Likely benign(5)

9 out of 10 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_001292063.2(OTOG):c.6074C>T (p.Ala2025Val)

Variation ID: 226902 Accession: VCV000226902.40

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 11p15.1 11: 17611374 (GRCh38) [ NCBI UCSC ] 11: 17632921 (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	May 29, 2016	Jan 11, 2026	Jan 9, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_001292063.2:c.6074C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001278992.1:p.Ala2025Val	missense
NM_001277269.2:c.6110C>T	NP_001264198.1:p.Ala2037Val	missense
NM_001277269.2:c.[6110C>T]
NC_000011.10:g.17611374C>T
NC_000011.9:g.17632921C>T
NG_033191.2:g.69002C>T

... more HGVS ... less HGVS

Protein change

A2037V, A2025V

Other names

Canonical SPDI

NC_000011.10:17611373:C:T

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.

0.00339 (T)

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

The Genome Aggregation Database (gnomAD), exomes 0.00134

The Genome Aggregation Database (gnomAD) 0.00229

The Genome Aggregation Database (gnomAD) 0.00240

The Genome Aggregation Database (gnomAD), exomes 0.00247

Trans-Omics for Precision Medicine (TOPMed) 0.00288

1000 Genomes Project 0.00339

1000 Genomes Project 30x 0.00359

Exome Aggregation Consortium (ExAC) 0.00374

Links

ClinGen: CA5905980 dbSNP: rs61736002 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.
OTOG		-	-	GRCh38 GRCh37	1453	1477

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/Likely benign (2)	criteria provided, multiple submitters, no conflicts	Sep 11, 2018	RCV000215530.8
not provided	Conflicting classifications of pathogenicity (5)	criteria provided, conflicting classifications	Jan 9, 2025	RCV000224482.30
Meniere disease	Uncertain significance (1)	criteria provided, single submitter	Jan 1, 2020	RCV001254787.2
Autosomal recessive nonsyndromic hearing loss 18B	Uncertain significance (1)	criteria provided, single submitter	Feb 28, 2019	RCV003133184.4
OTOG-related disorder	Likely benign (1)	no assertion criteria provided	May 21, 2020	RCV003977595.2

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 (Jul 31, 2018) C Contributing to aggregate classification	criteria provided, single submitter (Athena Diagnostics Criteria)	not provided	Athena Diagnostics Accession: SCV000842987.1 First in ClinVar: Jun 08, 2016 Last updated: Jun 08, 2016	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 02, 2016) C Contributing to aggregate classification	criteria provided, single submitter (LMM Criteria)	not specified	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV000269516.3 First in ClinVar: May 29, 2016 Last updated: May 29, 2016	Comment: show p.Ala2037Val in exon 35 of OTOG: This variant is not expected to have clinical s ignificance because it has been identified in 0.7% (36/5462) of South Asian chro mosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.or g; dbSNP rs61736002). (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: 3

Uncertain significance (Jan 01, 2020) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Meniere disease	Otology & Neurotology- Genomics of vestibular disorders (CTS-495), Jose Antonio López Escámez, Centro Pfizer - Universidad de Granada - Junta de Andalucía de Genómica e Investigación Oncológica (GENYO) Accession: SCV001167201.1 First in ClinVar: Aug 28, 2020 Last updated: Aug 28, 2020	Observation: 1 Collection method: case-control Allele origin: germline Affected status: yes more Observation 1 Collection method: case-control Allele origin: germline Affected status: yes Clinical Features: Sensorineural hearing loss (present) , Vertigo (present) , Tinnitus (present) Comment on clinical features: This variant was found in five Spanish MD cases from four unrelated families. Additionaly, this variant was found in a sporadic case. Three cases presented bilateral hearing loss and two showed unilateral hearing loss. The age at onset for these patients was 30-50 years old. Low and high frequency hearing had slight variations throughout the years. In familial MD patients, this variant was found along with the variant c.[805G>A] in OTOG gene. Platform type: whole-exome sequencing

Likely benign (Jul 22, 2021) C Contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Not Provided	GeneDx Accession: SCV001780656.1 First in ClinVar: Aug 13, 2021 Last updated: Aug 13, 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

Likely benign (Jan 09, 2025) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	not provided	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001122353.6 First in ClinVar: Dec 17, 2019 Last updated: Feb 25, 2025	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 (Sep 11, 2018) C Contributing to aggregate classification	criteria provided, single submitter (EGL ClinVar v180209 classification definitions)	not specified	Eurofins Ntd Llc (ga) Accession: SCV000863024.2 First in ClinVar: May 29, 2016 Last updated: Apr 13, 2025	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=OTOG Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Number of individuals with the variant: 1 Zygosity: Single Heterozygote Sex: mixed

Uncertain significance (May 12, 2016) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	not provided	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics Accession: SCV000280663.2 First in ClinVar: Jun 08, 2016 Last updated: Jun 08, 2025	Comment: show Converted during submission from Uncertain Significance to Uncertain significance. (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 Platform type: Sequencing Platform name: Illumina

Uncertain significance (Feb 28, 2019) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Autosomal recessive nonsyndromic hearing loss 18B	Revvity Omics, Revvity Accession: SCV003816541.3 First in ClinVar: Mar 04, 2023 Last updated: Sep 06, 2025	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 (Aug 01, 2024) 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: SCV005330327.12 First in ClinVar: Oct 08, 2024 Last updated: Jan 11, 2026	Comment: show OTOG: BP4 (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

Likely benign (May 21, 2020) N Not contributing to aggregate classification	no assertion criteria provided	OTOG-related condition	PreventionGenetics, part of Exact Sciences Accession: SCV004799391.2 First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024	Comment: show This variant is classified as likely 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

Comment:

p.Ala2037Val in exon 35 of OTOG: This variant is not expected to have clinical s ignificance because it has been identified in 0.7% (36/5462) of South Asian chro mosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.or g; dbSNP rs61736002).

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=OTOG	-	-	-	-

Text-mined citations for rs61736002 ...

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 Jan 11, 2026

ClinVar Genomic variation as it relates to human health

NM_001292063.2(OTOG):c.6074C>T (p.Ala2025Val)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Citations for germline classification of this variant

Text-mined citations for rs61736002 ...