ClinVar Genomic variation as it relates to human health
NM_005422.4(TECTA):c.4085G>A (p.Trp1362Ter)
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_005422.4(TECTA):c.4085G>A (p.Trp1362Ter)
Variation ID: 498538 Accession: VCV000498538.22
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11q23.3 11: 121146096 (GRCh38) [ NCBI UCSC ] 11: 121016805 (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 2, 2018 Feb 14, 2024 Jan 21, 2020 - HGVS
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Nucleotide Protein Molecular
consequenceNM_005422.4:c.4085G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_005413.2:p.Trp1362Ter nonsense NM_001378761.1:c.5042G>A NP_001365690.1:p.Trp1681Ter nonsense NM_005422.2(TECTA):c.4085G>A NC_000011.10:g.121146096G>A NC_000011.9:g.121016805G>A NG_011633.1:g.48431G>A - Protein change
- W1362*, W1681*
- Other names
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- Canonical SPDI
- NC_000011.10:121146095:G:A
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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.
Exome Aggregation Consortium (ExAC) 0.00003
The Genome Aggregation Database (gnomAD), exomes 0.00004
Trans-Omics for Precision Medicine (TOPMed) 0.00008
The Genome Aggregation Database (gnomAD) 0.00011
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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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
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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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TBCEL-TECTA | - | - | - | GRCh38 | - | 1060 |
TECTA | - | - |
GRCh38 GRCh37 |
- | 1067 |
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 (3) |
criteria provided, multiple submitters, no conflicts
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Jan 13, 2024 | RCV000593220.13 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Dec 4, 2018 | RCV000602678.5 | |
Uncertain significance (1) |
criteria provided, single submitter
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Apr 28, 2017 | RCV000778309.4 | |
Uncertain significance (1) |
criteria provided, single submitter
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Apr 28, 2017 | RCV000778310.4 | |
Pathogenic (1) |
reviewed by expert panel
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Jan 21, 2020 | RCV001089678.1 |
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
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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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Pathogenic
(Jan 21, 2020)
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reviewed by expert panel
Method: curation
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Nonsyndromic genetic hearing loss
Affected status: unknown
Allele origin:
germline
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ClinGen Hearing Loss Variant Curation Expert Panel
Accession: SCV001245162.1
First in ClinVar: May 04, 2020 Last updated: May 04, 2020 |
Comment:
The c.4085G>A (p.Trp1362Ter) nonsense variant in TECTA is predicted to cause a premature stop codon in biologically-relevant exon 11 of 23 total exons, leading to … (more)
The c.4085G>A (p.Trp1362Ter) nonsense variant in TECTA is predicted to cause a premature stop codon in biologically-relevant exon 11 of 23 total exons, leading to a truncated or absent protein in a gene in which loss of function is an established mechanism of autosomal recessive nonsyndromic hearing loss (PVS1; PMID: 30192042). This variant is present in 0.01121% (14/124864) of non-Finnish European chromosomes in gnomAD v2 (PM2_Supporting). It has been observed in at least two probands presenting with nonsyndromic hearing loss (PMID: 31163360; LMM internal data SCV000711208.2). One individual harbored another nonsense variant in TECTA, which was suspected to be pathogenic (PM3_Supporting). In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive nonsyndromic hearing loss. ACMG/AMP Criteria applied as specified by the Hearing Loss Expert Panel: PVS1, PM2_Supporting, PM3_Supporting. (less)
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Pathogenic
(Dec 07, 2016)
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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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Eurofins Ntd Llc (ga)
Accession: SCV000703594.2
First in ClinVar: Apr 02, 2018 Last updated: Apr 02, 2018 |
Number of individuals with the variant: 1
Sex: mixed
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Uncertain significance
(Apr 28, 2017)
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criteria provided, single submitter
Method: clinical testing
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Autosomal dominant nonsyndromic hearing loss 12
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000914492.1
First in ClinVar: May 27, 2019 Last updated: May 27, 2019 |
Comment:
The TECTA c.4085G>A (p.Trp1362Ter) variant is a stop-gained variant predicted to result in premature termination of the protein. The variant was observed by ICSL as … (more)
The TECTA c.4085G>A (p.Trp1362Ter) variant is a stop-gained variant predicted to result in premature termination of the protein. The variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018) and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score for this variant, it could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. Due to the potential impact of stop-gained variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for a dominant form of nonsyndromic hearing loss. (less)
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Uncertain significance
(Apr 28, 2017)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive nonsyndromic hearing loss 21
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000914493.1
First in ClinVar: May 27, 2019 Last updated: May 27, 2019 |
Comment:
The TECTA c.4085G>A (p.Trp1362Ter) variant is a stop-gained variant predicted to result in premature termination of the protein. The variant was observed by ICSL as … (more)
The TECTA c.4085G>A (p.Trp1362Ter) variant is a stop-gained variant predicted to result in premature termination of the protein. The variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018) and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score for this variant, it could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. Due to the potential impact of stop-gained variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for a recessive form of nonsyndromic hearing loss. (less)
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Likely pathogenic
(Dec 04, 2018)
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criteria provided, single submitter
Method: clinical testing
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Rare genetic deafness
(Autosomal recessive inheritance)
Affected status: not provided
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000711208.2
First in ClinVar: Apr 09, 2018 Last updated: Aug 26, 2019 |
Comment:
The p.Trp1362X variant in TECTA has been identified in the heterozygous state in 1 family with hearing loss; however, this family also harbored pathogenic varia … (more)
The p.Trp1362X variant in TECTA has been identified in the heterozygous state in 1 family with hearing loss; however, this family also harbored pathogenic varia nts in different genes that may explain their hearing loss (LMM data). The p.Trp 1362X variant has also been identified in 0.01% (14/124864) of European chromoso mes by gnomAD (http://gnomad.broadinstitute.org) and has been reported in ClinVa r (Variation ID 498538). Although this variant has been seen in the general popu lation, its frequency is low enough to be consistent with a recessive carrier fr equency. This nonsense variant leads to a premature termination codon at positio n 1362, which is predicted to lead to a truncated or absent protein. Loss of fun ction of the TECTA gene is an established disease mechanism in autosomal recessi ve hearing loss (Hildebrand 2011). In summary, this variant meets criteria to be classified as likely pathogenic for autosomal recessive hearing loss. ACMG/AMP criteria applied: PVS1, PM2_Supporting. Please note that some truncating variant s in TECTA have been reported to segregate in an autosomal dominant manner (Coli n 2008, Hildebrand 2011); however, there is currently insufficient data to predi ct whether the p.Trp1362X variant can lead to dominantly inherited hearing loss. (less)
Number of individuals with the variant: 5
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Likely pathogenic
(Nov 16, 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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GeneDx
Accession: SCV001829314.3
First in ClinVar: Sep 08, 2021 Last updated: Dec 03, 2022 |
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: 31163360) (less)
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Pathogenic
(Jan 13, 2024)
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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: SCV001584375.4
First in ClinVar: May 10, 2021 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Trp1362*) in the TECTA gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Trp1362*) in the TECTA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TECTA are known to be pathogenic (PMID: 11087000, 12746400, 17431902, 24130743). This variant is present in population databases (rs199638531, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with non-syndromic deafness (PMID: 31163360). ClinVar contains an entry for this variant (Variation ID: 498538). For these reasons, this variant has been classified as Pathogenic. (less)
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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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Genetic testing for congenital non-syndromic sensorineural hearing loss. | Raymond M | International journal of pediatric otorhinolaryngology | 2019 | PMID: 31163360 |
Massively parallel DNA sequencing successfully identifies new causative mutations in deafness genes in patients with cochlear implantation and EAS. | Miyagawa M | PloS one | 2013 | PMID: 24130743 |
Identification of three novel TECTA mutations in Iranian families with autosomal recessive nonsyndromic hearing impairment at the DFNB21 locus. | Meyer NC | American journal of medical genetics. Part A | 2007 | PMID: 17431902 |
Distinctive audiometric profile associated with DFNB21 alleles of TECTA. | Naz S | Journal of medical genetics | 2003 | PMID: 12746400 |
A targeted deletion in alpha-tectorin reveals that the tectorial membrane is required for the gain and timing of cochlear feedback. | Legan PK | Neuron | 2000 | PMID: 11087000 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=TECTA | - | - | - | - |
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/3cef6ced-0d25-4c76-9b45-dc177c59acc4 | - | - | - | - |
Text-mined citations for rs199638531 ...
HelpRecord last updated Feb 20, 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.