ClinVar Genomic variation as it relates to human health
NM_001292063.2(OTOG):c.2464C>T (p.Gln822Ter)
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.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001292063.2(OTOG):c.2464C>T (p.Gln822Ter)
Variation ID: 417941 Accession: VCV000417941.45
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11p15.1 11: 17574890 (GRCh38) [ NCBI UCSC ] 11: 17596437 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Apr 23, 2017 May 12, 2024 Oct 24, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001292063.2:c.2464C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001278992.1:p.Gln822Ter nonsense NM_001277269.2:c.2500C>T NP_001264198.1:p.Gln834Ter nonsense NC_000011.10:g.17574890C>T NC_000011.9:g.17596437C>T NG_033191.2:g.32518C>T - Protein change
- Q834*, Q822*
- Other names
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- Canonical SPDI
- NC_000011.10:17574889:C:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe 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.
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Allele frequency
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The frequency of the allele represented by this VCV record.
Trans-Omics for Precision Medicine (TOPMed) 0.00035
The Genome Aggregation Database (gnomAD), exomes 0.00038
The Genome Aggregation Database (gnomAD) 0.00040
Exome Aggregation Consortium (ExAC) 0.00076
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 | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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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. |
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OTOG | - | - |
GRCh38 GRCh37 |
1249 | 1272 |
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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic/Likely pathogenic (5) |
criteria provided, multiple submitters, no conflicts
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Jul 26, 2022 | RCV000477813.12 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Oct 24, 2023 | RCV000578779.27 | |
Pathogenic (1) |
criteria provided, single submitter
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Apr 14, 2020 | RCV000616086.8 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Feb 7, 2019 | RCV001007897.3 |
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. |
More information
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. |
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Likely pathogenic
(Feb 07, 2019)
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criteria provided, single submitter
Method: clinical testing
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Intellectual disability
Seizure (Autosomal recessive inheritance)
Affected status: yes
Allele origin:
maternal
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Genomic Medicine Lab, University of California San Francisco
Study: CSER
Accession: SCV001167603.1 First in ClinVar: Mar 16, 2020 Last updated: Mar 16, 2020 |
Sex: female
Secondary finding: no
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Pathogenic
(Apr 14, 2020)
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criteria provided, single submitter
Method: clinical testing
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Rare genetic deafness
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000712161.3
First in ClinVar: Apr 09, 2018 Last updated: Jul 03, 2020 |
Comment:
The p.Gln834X variant in OTOG has been identified in 4 individuals with hearing loss: 2 heterozygotes where a second variant was not identified on the … (more)
The p.Gln834X variant in OTOG has been identified in 4 individuals with hearing loss: 2 heterozygotes where a second variant was not identified on the other copy of OTOG, in 1 homozygote, and in 1 compound heterozygote with a second pathogenic OTOG variant (Sheppard 2018 PMID: 29907799, LMM data). Both variants segregated with hearing loss in an affected sibling (LMM data). The p.Gln834X variant has also been reported by other clinical laboratories in ClinVar (Variation ID 417941) and has been identified in 0.12% (8/6636) of Ashkenazi Jewish and in 0.08% (51/60760) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org); however, this frequency is not high enough to rule out a pathogenic role. This nonsense variant leads to a premature termination codon at position 834, which is predicted to lead to a truncated or absent protein. Loss of function of the OTOG gene is an established disease mechanism in autosomal recessive hearing loss. In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive hearing loss. ACMG/AMP Criteria applied: PVS1, PM3, PP1, BS1_Supporting. (less)
Number of individuals with the variant: 6
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Pathogenic
(Jul 22, 2021)
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criteria provided, single submitter
Method: research
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Autosomal recessive nonsyndromic hearing loss 18B
Affected status: yes
Allele origin:
maternal
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HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology
Study: AGHI WGS
Accession: SCV001870382.1 First in ClinVar: Sep 19, 2021 Last updated: Sep 19, 2021 |
Comment:
ACMG codes:PVS1, PM2, PP5
Number of individuals with the variant: 1
Clinical Features:
Hearing impairment (present) , Delayed speech and language development (present) , Global developmental delay (present) , Tachycardia (present)
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Pathogenic
(Jul 26, 2022)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive nonsyndromic hearing loss 18B
Affected status: yes
Allele origin:
inherited
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Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV002576464.1
First in ClinVar: Oct 01, 2022 Last updated: Oct 01, 2022 |
Comment:
This variant was identified as homozygous._x000D_ Criteria applied: PVS1, PM3_STR
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Likely pathogenic
(Jul 10, 2021)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive nonsyndromic hearing loss 18B
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV000893872.2
First in ClinVar: Mar 31, 2019 Last updated: Dec 31, 2022 |
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Pathogenic
(Dec 10, 2021)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000680934.4
First in ClinVar: Feb 13, 2018 Last updated: Mar 04, 2023 |
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This … (more)
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 10655058, 29907799, 32860223, 33105617, 34426522) (less)
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Likely pathogenic
(Jan 24, 2022)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive nonsyndromic hearing loss 18B
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV002020598.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(Oct 24, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001206868.4
First in ClinVar: Apr 15, 2020 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Gln834*) in the OTOG gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Gln834*) in the OTOG gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in OTOG are known to be pathogenic (PMID: 23122587). This variant is present in population databases (rs554847663, gnomAD 0.1%). This premature translational stop signal has been observed in individual(s) with clinical features of autosomal recessive deafness (PMID: 29907799). ClinVar contains an entry for this variant (Variation ID: 417941). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Jun 01, 2022)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV000891954.23
First in ClinVar: Mar 31, 2019 Last updated: May 12, 2024 |
Comment:
OTOG: PVS1, PM2
Number of individuals with the variant: 8
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Likely pathogenic
(Jul 19, 2016)
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no assertion criteria provided
Method: research
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Autosomal recessive nonsyndromic hearing loss 18B
Affected status: yes
Allele origin:
germline
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Division of Human Genetics, Children's Hospital of Philadelphia
Study: CSER-PediSeq
Accession: SCV000536895.1 First in ClinVar: Apr 23, 2017 Last updated: Apr 23, 2017 |
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Utility and limitations of exome sequencing as a genetic diagnostic tool for children with hearing loss. | Sheppard S | Genetics in medicine : official journal of the American College of Medical Genetics | 2018 | PMID: 29907799 |
Mutations of the gene encoding otogelin are a cause of autosomal-recessive nonsyndromic moderate hearing impairment. | Schraders M | American journal of human genetics | 2012 | PMID: 23122587 |
Targeted disruption of otog results in deafness and severe imbalance. | Simmler MC | Nature genetics | 2000 | PMID: 10655058 |
Text-mined citations for rs554847663 ...
HelpRecord last updated May 12, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.