NM_007375.4(TARDBP):c.1122T>G (p.Tyr374Ter) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 10, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001855018.4

Allele description [Variation Report for NM_007375.4(TARDBP):c.1122T>G (p.Tyr374Ter)]

NM_007375.4(TARDBP):c.1122T>G (p.Tyr374Ter)

Gene:

TARDBP:TAR DNA binding protein [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p36.22

Genomic location:

Preferred name:

NM_007375.4(TARDBP):c.1122T>G (p.Tyr374Ter)

HGVS:

NC_000001.11:g.11022531T>G
NG_008734.1:g.14910T>G
NM_007375.4:c.1122T>GMANE SELECT
NP_031401.1:p.Tyr374Ter
NP_031401.1:p.Tyr374Ter
LRG_659t1:c.1122T>G
LRG_659:g.14910T>G
LRG_659p1:p.Tyr374Ter
NC_000001.10:g.11082588T>G
NM_007375.3:c.1122T>G

Protein change:

Y374*

Links:

dbSNP: rs147795017

NCBI 1000 Genomes Browser:

rs147795017

Molecular consequence:

NM_007375.4:c.1122T>G - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Amyotrophic lateral sclerosis type 10 (ALS10)
Synonyms:: AMYOTROPHIC LATERAL SCLEROSIS 10 WITH OR WITHOUT FRONTOTEMPORAL DEMENTIA; TARDBP-Related Amyotrophic Lateral Sclerosis; AMYOTROPHIC LATERAL SCLEROSIS 10 WITHOUT FRONTOTEMPORAL DEMENTIA AND WITH TDP43 INCLUSIONS; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0012790; MedGen: C2677565; Orphanet: 275872; Orphanet: 803; OMIM: 612069

Name:: TARDBP-related frontotemporal dementia
Synonyms:: FRONTOTEMPORAL LOBAR DEGENERATION WITH TDP43 INCLUSIONS, TARDBP-RELATED
Identifiers:: MedGen: C3150169

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002176105	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 10, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 18931000, 28089114, 28430856, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002176105

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 10, 2022)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Contribution of TARDBP mutations to sporadic amyotrophic lateral sclerosis.

Daoud H, Valdmanis PN, Kabashi E, Dion P, Dupré N, Camu W, Meininger V, Rouleau GA.

J Med Genet. 2009 Feb;46(2):112-4. doi: 10.1136/jmg.2008.062463. Epub 2008 Oct 17.

PubMed [citation]

PMID:: 18931000

Genetic epidemiology of motor neuron disease-associated variants in the Scottish population.

Black HA, Leighton DJ, Cleary EM, Rose E, Stephenson L, Colville S, Ross D, Warner J, Porteous M, Gorrie GH, Swingler R, Goldstein D, Harms MB, Connick P, Pal S, Aitman TJ, Chandran S.

Neurobiol Aging. 2017 Mar;51:178.e11-178.e20. doi: 10.1016/j.neurobiolaging.2016.12.013. Epub 2016 Dec 21. Erratum in: Neurobiol Aging. 2017 Aug;56:214. doi: 10.1016/j.neurobiolaging.2017.04.019.

PubMed [citation]

PMID:: 28089114
PMCID:: PMC5302213

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002176105.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 266065). This premature translational stop signal has been observed in individual(s) with TARDBP-related conditions (PMID: 18931000, 28089114, 28430856). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr374*) in the TARDBP gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 41 amino acid(s) of the TARDBP protein.

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

Last Updated: Sep 29, 2024

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Relating variation to medicine