NM_000360.4(TH):c.78del (p.Glu27fs) AND Autosomal recessive DOPA responsive dystonia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 25, 2019
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:: RCV001217693.6

Allele description [Variation Report for NM_000360.4(TH):c.78del (p.Glu27fs)]

NM_000360.4(TH):c.78del (p.Glu27fs)

Gene:

TH:tyrosine hydroxylase [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

11p15.5

Genomic location:

Preferred name:

NM_000360.4(TH):c.78del (p.Glu27fs)

HGVS:

NC_000011.10:g.2171709del
NG_008128.1:g.5097del
NM_000360.4:c.78delMANE SELECT
NM_199292.3:c.78del
NM_199293.3:c.78del
NP_000351.2:p.Glu27fs
NP_954986.2:p.Glu27fs
NP_954987.2:p.Glu27fs
NC_000011.9:g.2192939del
NM_199292.2:c.78del

Protein change:

E27fs

Links:

dbSNP: rs1846263622

NCBI 1000 Genomes Browser:

rs1846263622

Molecular consequence:

NM_000360.4:c.78del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_199292.3:c.78del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_199293.3:c.78del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Autosomal recessive DOPA responsive dystonia
Synonyms:: Segawa syndrome, autosomal recessive; DYT-TH; TH-deficient dopa-responsive dystonia; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0011551; MedGen: C2673535; Orphanet: 101150; OMIM: 605407

Recent activity

Clear Turn Off Turn On

Rhizobium sp. AJEPHGR 25 isolate:HGR 25
Rhizobium sp. AJEPHGR 25 isolate:HGR 25
Rhizobium sp. AJEPHGR 25 isolate:HGR 25 Genome sequencing and assembly

BioProject
Measles virus genotype D8 MVs/Osaka.JPN/10.24[D8] viral cRNA, M-F intergenic spa...
Measles virus genotype D8 MVs/Osaka.JPN/10.24[D8] viral cRNA, M-F intergenic spacer
gi|2715817008|dbj|LC810427.1|

Nucleotide
Linked optical and gene expression profiling of single cells at high throughput
Linked optical and gene expression profiling of single cells at high throughput
Linked optical and gene expression profiling of single cells at high throughput

BioProject
Triticum aestivum cultivar:BTS
Triticum aestivum cultivar:BTS
Triticum aestivum cultivar:BTS Raw sequence reads

BioProject

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001389542	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 25, 2019)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 22264700, 24753243, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001389542

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 25, 2019)

germline

clinical testing

PubMed (3)
[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

Tyrosine hydroxylase deficiency in Taiwanese infants.

Chi CS, Lee HF, Tsai CR.

Pediatr Neurol. 2012 Feb;46(2):77-82. doi: 10.1016/j.pediatrneurol.2011.11.012.

PubMed [citation]

PMID:: 22264700

Functional studies of tyrosine hydroxylase missense variants reveal distinct patterns of molecular defects in Dopa-responsive dystonia.

Fossbakk A, Kleppe R, Knappskog PM, Martinez A, Haavik J.

Hum Mutat. 2014 Jul;35(7):880-90. doi: 10.1002/humu.22565. Epub 2014 Jun 3.

PubMed [citation]

PMID:: 24753243
PMCID:: PMC4312968

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001389542.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in TH are known to be pathogenic (PMID: 22264700, 24753243). This variant has not been reported in the literature in individuals with TH-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Glu27Argfs*5) in the TH gene. It is expected to result in an absent or disrupted protein product.

#	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

ClinVar

Relating variation to medicine