NM_007375.4(TARDBP):c.1147A>G (p.Ile383Val) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 16, 2023
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:: RCV001851976.5

Allele description [Variation Report for NM_007375.4(TARDBP):c.1147A>G (p.Ile383Val)]

NM_007375.4(TARDBP):c.1147A>G (p.Ile383Val)

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.1147A>G (p.Ile383Val)

HGVS:

NC_000001.11:g.11022556A>G
NG_008734.1:g.14935A>G
NM_007375.4:c.1147A>GMANE SELECT
NP_031401.1:p.Ile383Val
NP_031401.1:p.Ile383Val
LRG_659t1:c.1147A>G
LRG_659:g.14935A>G
LRG_659p1:p.Ile383Val
NC_000001.10:g.11082613A>G
NM_007375.3:c.1147A>G

Protein change:

I383V

Links:

dbSNP: rs80356740

NCBI 1000 Genomes Browser:

rs80356740

Molecular consequence:

NM_007375.4:c.1147A>G - missense variant - [Sequence Ontology: SO:0001583]

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
SCV002235625	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 16, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 25681989, 26581115, 30773994, 33159016, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002235625

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 16, 2023)

germline

clinical testing

PubMed (5)
[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

The distinct genetic pattern of ALS in Turkey and novel mutations.

Özoğuz A, Uyan Ö, Birdal G, Iskender C, Kartal E, Lahut S, Ömür Ö, Agim ZS, Eken AG, Sen NE, Kavak P, Saygı C, Sapp PC, Keagle P, Parman Y, Tan E, Koç F, Deymeer F, Oflazer P, Hanağası H, Gürvit H, Bilgiç B, et al.

Neurobiol Aging. 2015 Apr;36(4):1764.e9-1764.e18. doi: 10.1016/j.neurobiolaging.2014.12.032. Epub 2015 Jan 10.

PubMed [citation]

PMID:: 25681989
PMCID:: PMC6591733

A single nucleotide TDP-43 mutation within a Taiwanese family: A multifaceted demon.

Cheng YW, Lee MJ, Chen TF, Cheng TW, Lai YM, Hua MS, Chiu MJ.

Amyotroph Lateral Scler Frontotemporal Degener. 2016;17(3-4):292-4. doi: 10.3109/21678421.2015.1111905. Epub 2015 Nov 19. No abstract available.

PubMed [citation]

PMID:: 26581115

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002235625.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬†is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 21476). This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 383 of the TARDBP protein (p.Ile383Val). This variant is present in population databases (rs80356740, gnomAD 0.008%). This missense change has been observed in individuals with amyotrophic lateral sclerosis and/or frontotemporal lobar degeneration (PMID: 25681989, 26581115, 30773994, 33159016). It has also been observed to segregate with disease in related individuals.

#	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: Oct 20, 2024

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