ClinVar Genomic variation as it relates to human health
NM_007375.4(TARDBP):c.198T>C (p.Ala66=)
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_007375.4(TARDBP):c.198T>C (p.Ala66=)
Variation ID: 291734 Accession: VCV000291734.77
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 1p36.22 1: 11013925 (GRCh38) [ NCBI UCSC ] 1: 11073982 (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 Dec 6, 2016 Oct 20, 2024 Jan 27, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_007375.4:c.198T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_031401.1:p.Ala66= synonymous NC_000001.11:g.11013925T>C NC_000001.10:g.11073982T>C NG_008734.1:g.6304T>C LRG_659:g.6304T>C LRG_659t1:c.198T>C LRG_659p1:p.Ala66= - Protein change
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- Other names
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- Canonical SPDI
- NC_000001.11:11013924:T:C
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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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0.00519 (C)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
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The Genome Aggregation Database (gnomAD) 0.00292
Trans-Omics for Precision Medicine (TOPMed) 0.00352
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00438
1000 Genomes Project 30x 0.00484
1000 Genomes Project 0.00519
Exome Aggregation Consortium (ExAC) 0.00641
- Links
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
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. |
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TARDBP | No evidence available | No evidence available |
GRCh38 GRCh37 |
246 | 360 |
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. |
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Benign (1) |
criteria provided, single submitter
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Jul 25, 2017 | RCV000516412.12 | |
Benign (1) |
criteria provided, single submitter
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Jan 27, 2024 | RCV000646151.20 | |
Benign/Likely benign (5) |
criteria provided, multiple submitters, no conflicts
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Jul 15, 2021 | RCV000625045.18 | |
Benign/Likely benign (5) |
criteria provided, multiple submitters, no conflicts
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Oct 1, 2023 | RCV001668630.29 | |
Likely benign (1) |
criteria provided, single submitter
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May 19, 2022 | RCV002418140.9 |
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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Benign
(Jul 25, 2017)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Athena Diagnostics
Accession: SCV000615748.1
First in ClinVar: Dec 19, 2017 Last updated: Dec 19, 2017 |
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Likely benign
(Jun 28, 2017)
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criteria provided, single submitter
Method: clinical testing
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Amyotrophic lateral sclerosis type 10
Affected status: yes
Allele origin:
germline
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Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Study: VKGL Data-share Consensus
Accession: SCV000744937.1 First in ClinVar: Apr 20, 2018 Last updated: Apr 20, 2018 |
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Benign
(Oct 10, 2014)
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criteria provided, single submitter
Method: clinical testing
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Amyotrophic lateral sclerosis type 10
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, University Medical Center Utrecht
Study: VKGL Data-share Consensus
Accession: SCV000743618.1 First in ClinVar: Apr 20, 2018 Last updated: Apr 20, 2018 |
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Likely benign
(Apr 27, 2017)
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criteria provided, single submitter
Method: clinical testing
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Amyotrophic lateral sclerosis type 10
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000347104.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
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Benign
(Jan 09, 2020)
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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: SCV001890008.1
First in ClinVar: Sep 19, 2021 Last updated: Sep 19, 2021 |
Comment:
This variant is associated with the following publications: (PMID: 18545701, 25588603)
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Benign
(Jul 15, 2021)
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criteria provided, single submitter
Method: clinical testing
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Amyotrophic lateral sclerosis type 10
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV002062211.1
First in ClinVar: Jan 29, 2022 Last updated: Jan 29, 2022 |
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Benign
(Sep 22, 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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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV001159167.3
First in ClinVar: Feb 10, 2020 Last updated: Feb 20, 2024 |
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Benign
(Jan 27, 2024)
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criteria provided, single submitter
Method: clinical testing
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Amyotrophic lateral sclerosis type 10
TARDBP-related frontotemporal dementia
Explanation for multiple conditions: Uncertain.
The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000767909.8
First in ClinVar: May 28, 2018 Last updated: Feb 28, 2024 |
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Likely benign
(May 19, 2022)
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criteria provided, single submitter
Method: clinical testing
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Inborn genetic diseases
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV002717583.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more)
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
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Benign
(Oct 01, 2023)
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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: SCV003916049.13
First in ClinVar: Apr 23, 2023 Last updated: Oct 20, 2024 |
Comment:
TARDBP: BP4, BP7, BS1, BS2
Number of individuals with the variant: 7
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Likely benign
(-)
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criteria provided, single submitter
Method: not provided
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not provided
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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Breakthrough Genomics, Breakthrough Genomics
Accession: SCV005260660.1
First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024 |
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Likely benign
(Dec 29, 2015)
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no assertion criteria provided
Method: clinical testing
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Amyotrophic lateral sclerosis type 10
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, Amsterdam University Medical Center
Study: VKGL Data-share Consensus
Accession: SCV000745748.1 First in ClinVar: Apr 20, 2018 Last updated: Apr 20, 2018 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics, Academic Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001921792.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
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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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Investigation of next-generation sequencing technologies as a diagnostic tool for amyotrophic lateral sclerosis. | Morgan S | Neurobiology of aging | 2015 | PMID: 25588603 |
TARDBP mutations in frontotemporal lobar degeneration: frequency, clinical features, and disease course. | Borroni B | Rejuvenation research | 2010 | PMID: 20645878 |
Broad clinical phenotypes associated with TAR-DNA binding protein (TARDBP) mutations in amyotrophic lateral sclerosis. | Kirby J | Neurogenetics | 2010 | PMID: 19760257 |
TARDBP in amyotrophic lateral sclerosis: identification of a novel variant but absence of copy number variation. | Bäumer D | Journal of neurology, neurosurgery, and psychiatry | 2009 | PMID: 19864663 |
Mutations in TDP-43 link glycine-rich domain functions to amyotrophic lateral sclerosis. | Pesiridis GS | Human molecular genetics | 2009 | PMID: 19808791 |
Absence of TARDBP gene mutations in an italian series of patients with frontotemporal lobar degeneration. | Gallone S | Dementia and geriatric cognitive disorders | 2009 | PMID: 19786775 |
Genetic variants in the promoter of TARDBP in sporadic amyotrophic lateral sclerosis. | Luquin N | Neuromuscular disorders : NMD | 2009 | PMID: 19695877 |
TARDBP (TDP-43) sequence analysis in patients with familial and sporadic ALS: identification of two novel mutations. | Del Bo R | European journal of neurology | 2009 | PMID: 19236453 |
High frequency of TARDBP gene mutations in Italian patients with amyotrophic lateral sclerosis. | Corrado L | Human mutation | 2009 | PMID: 19224587 |
No TARDBP mutations in a French Canadian population of patients with Parkinson disease. | Kabashi E | Archives of neurology | 2009 | PMID: 19204172 |
Contribution of TARDBP mutations to sporadic amyotrophic lateral sclerosis. | Daoud H | Journal of medical genetics | 2009 | PMID: 18931000 |
Neuronal inclusion protein TDP-43 has no primary genetic role in FTD and ALS. | Gijselinck I | Neurobiology of aging | 2009 | PMID: 18068872 |
Novel mutations in TARDBP (TDP-43) in patients with familial amyotrophic lateral sclerosis. | Rutherford NJ | PLoS genetics | 2008 | PMID: 18802454 |
Two German kindreds with familial amyotrophic lateral sclerosis due to TARDBP mutations. | Kühnlein P | Archives of neurology | 2008 | PMID: 18779421 |
TDP-43 is not a common cause of sporadic amyotrophic lateral sclerosis. | Guerreiro RJ | PloS one | 2008 | PMID: 18545701 |
TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis. | Kabashi E | Nature genetics | 2008 | PMID: 18372902 |
TDP-43 A315T mutation in familial motor neuron disease. | Gitcho MA | Annals of neurology | 2008 | PMID: 18288693 |
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Text-mined citations for rs61730366 ...
HelpRecord last updated Oct 27, 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.