NM_000360.4(TH):c.241G>A (p.Val81Met) AND Autosomal recessive DOPA responsive dystonia

Germline classification:: Benign (7 submissions)
Last evaluated:: Feb 4, 2025
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000021078.23

Allele description [Variation Report for NM_000360.4(TH):c.241G>A (p.Val81Met)]

NM_000360.4(TH):c.241G>A (p.Val81Met)

Gene:

TH:tyrosine hydroxylase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11p15.5

Genomic location:

Preferred name:

NM_000360.4(TH):c.241G>A (p.Val81Met)

HGVS:

NC_000011.10:g.2169721C>T
NG_008128.1:g.7085G>A
NM_000360.4:c.241G>AMANE SELECT
NM_199292.3:c.334G>A
NM_199293.3:c.322G>A
NP_000351.2:p.Val81Met
NP_954986.2:p.Val112Met
NP_954987.2:p.Val108Met
NC_000011.9:g.2190951C>T
NM_000360.3:c.241G>A
NM_199292.2:c.334G>A
P07101:p.Val112Met

Protein change:

V108M

Links:

UniProtKB: P07101#VAR_014025; dbSNP: rs6356

NCBI 1000 Genomes Browser:

rs6356

Molecular consequence:

NM_000360.4:c.241G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_199292.3:c.334G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_199293.3:c.322G>A - missense variant - [Sequence Ontology: SO:0001583]

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000041738	GeneReviews	no classification provided	not provided	unknown	literature only	PubMed (3) [See all records that cite these PMIDs] 7789962, 9754624, 20301610
SCV000369930	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Benign (Jan 12, 2018)	germline	clinical testing	Citation Link,
SCV000745021	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus	criteria provided, single submitter (ACGS Guidelines, 2013)	Benign (Sep 21, 2015)	germline	clinical testing	Citation Link,
SCV000745786	Genome Diagnostics Laboratory, Amsterdam University Medical Center - VKGL Data-share Consensus	no assertion criteria provided (ACGS Guidelines, 2013)	Benign (Feb 7, 2015)	germline	clinical testing	Citation Link,
SCV001463823	Natera, Inc.	no assertion criteria provided	Benign (Sep 16, 2020)	germline	clinical testing
SCV001725244	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Benign (Feb 4, 2025)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001754956	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign (Jul 10, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Frequent sequence variant in the human tyrosine hydroxylase gene.

Lüdecke B, Bartholomé K.

Hum Genet. 1995 Jun;95(6):716.

PubMed [citation]

PMID:: 7789962

Systematic search for variations in the tyrosine hydroxylase gene and their associations with schizophrenia, affective disorders, and alcoholism.

Ishiguro H, Arinami T, Saito T, Akazawa S, Enomoto M, Mitushio H, Fujishiro H, Tada K, Akimoto Y, Mifune H, Shiozuka S, Hamaguchi H, Toru M, Shibuya H.

Am J Med Genet. 1998 Sep 7;81(5):388-96.

PubMed [citation]

PMID:: 9754624

See all PubMed Citations (5)

Details of each submission

From GeneReviews, SCV000041738.2

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

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

From Illumina Laboratory Services, Illumina, SCV000369930.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

This variant was observed in the ICSL laboratory 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

#	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

From Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus, SCV000745021.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

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

From Genome Diagnostics Laboratory, Amsterdam University Medical Center - VKGL Data-share Consensus, SCV000745786.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

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

From Natera, Inc., SCV001463823.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001725244.5

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

#	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

From Genome-Nilou Lab, SCV001754956.2

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 13, 2025

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