NM_001082971.2(DDC):c.1039C>T (p.Arg347Trp) AND Deficiency of aromatic-L-amino-acid decarboxylase

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 20, 2021
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:: RCV001367572.7

Allele description [Variation Report for NM_001082971.2(DDC):c.1039C>T (p.Arg347Trp)]

NM_001082971.2(DDC):c.1039C>T (p.Arg347Trp)

Gene:

DDC:dopa decarboxylase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p12.2

Genomic location:

Preferred name:

NM_001082971.2(DDC):c.1039C>T (p.Arg347Trp)

HGVS:

NC_000007.14:g.50476626G>A
NG_008742.1:g.93831C>T
NM_000790.4:c.1039C>T
NM_001082971.2:c.1039C>TMANE SELECT
NM_001242886.2:c.925C>T
NM_001242887.2:c.895C>T
NM_001242888.2:c.805C>T
NM_001242889.2:c.760C>T
NP_000781.2:p.Arg347Trp
NP_001076440.2:p.Arg347Trp
NP_001229815.2:p.Arg309Trp
NP_001229816.2:p.Arg299Trp
NP_001229817.2:p.Arg269Trp
NP_001229818.2:p.Arg254Trp
NC_000007.13:g.50544324G>A

Protein change:

R254W

Links:

dbSNP: rs773990125

NCBI 1000 Genomes Browser:

rs773990125

Molecular consequence:

NM_000790.4:c.1039C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001082971.2:c.1039C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001242886.2:c.925C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001242887.2:c.895C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001242888.2:c.805C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001242889.2:c.760C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Deficiency of aromatic-L-amino-acid decarboxylase
Synonyms:: DDC deficiency; Aromatic amino acid decarboxylase deficiency; Dopa decarboxylase deficiency
Identifiers:: MONDO: MONDO:0012084; MedGen: C1291564; Orphanet: 35708; OMIM: 608643

Recent activity

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mitochondrial carnitine/acylcarnitine carrier-like protein [Lycium barbarum]
mitochondrial carnitine/acylcarnitine carrier-like protein [Lycium barbarum]
gi|2599348783|ref|XP_060177453.1|

Protein
S41 family peptidase [Bradyrhizobium sp. C-145]
S41 family peptidase [Bradyrhizobium sp. C-145]
gi|2239578550|gnl|PRJNA782308|LRP30 5|gb|UQR63945.1|

Protein
LOC109735056 [Aegilops tauschii]
LOC109735056 [Aegilops tauschii]
Gene ID:109735056

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001563926	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 20, 2021)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 17240182, 23430870, 24865461, 30144970, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001563926

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 20, 2021)

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

Aromatic L-amino acid decarboxylase enzyme activity in deficient patients and heterozygotes.

Verbeek MM, Geurtz PB, Willemsen MA, Wevers RA.

Mol Genet Metab. 2007 Apr;90(4):363-9. Epub 2007 Jan 19.

PubMed [citation]

PMID:: 17240182

Kinetic analyses guide the therapeutic decision in a novel form of moderate aromatic Acid decarboxylase deficiency.

Barth M, Serre V, Hubert L, Chaabouni Y, Bahi-Buisson N, Cadoudal M, Rabier D, Tich SN, Ribeiro M, Ricquier D, Munnich A, Bonneau D, de Lonlay P, Christa L.

JIMD Rep. 2012;3:25-32. doi: 10.1007/8904_2011_43. Epub 2011 Sep 16.

PubMed [citation]

PMID:: 23430870
PMCID:: PMC3520504

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001563926.4

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

Description

ClinVar contains an entry for this variant (Variation ID: 1058431). 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. This variant disrupts the p.Arg347 amino acid residue in DDC. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 17240182, 23430870, 24865461, 30144970). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with DDC-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 347 of the DDC protein (p.Arg347Trp).

#	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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