NM_001082971.2(DDC):c.1339C>A (p.Arg447Ser) AND Deficiency of aromatic-L-amino-acid decarboxylase

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 25, 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:: RCV002852032.3

Allele description [Variation Report for NM_001082971.2(DDC):c.1339C>A (p.Arg447Ser)]

NM_001082971.2(DDC):c.1339C>A (p.Arg447Ser)

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.1339C>A (p.Arg447Ser)

HGVS:

NC_000007.14:g.50463335G>T
NG_008742.1:g.107122C>A
NG_008742.2:g.107070C>A
NM_000790.4:c.1339C>A
NM_001082971.2:c.1339C>AMANE SELECT
NM_001242886.2:c.1225C>A
NM_001242887.2:c.1195C>A
NM_001242888.2:c.1105C>A
NM_001242889.2:c.1060C>A
NP_000781.2:p.Arg447Ser
NP_001076440.2:p.Arg447Ser
NP_001229815.2:p.Arg409Ser
NP_001229816.2:p.Arg399Ser
NP_001229817.2:p.Arg369Ser
NP_001229818.2:p.Arg354Ser
NC_000007.13:g.50531033G>T

Protein change:

R354S

Molecular consequence:

NM_000790.4:c.1339C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001082971.2:c.1339C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001242886.2:c.1225C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001242887.2:c.1195C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001242888.2:c.1105C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001242889.2:c.1060C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Deficiency of aromatic-L-amino-acid decarboxylase
Synonyms:: AADC DEFICIENCY; DDC DEFICIENCY; DOPA DECARBOXYLASE DEFICIENCY; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0012084; MedGen: C1291564; Orphanet: 35708; OMIM: 608643

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003223952	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 25, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 17240182, 32409695, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003223952

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 25, 2022)

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

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

The genetic and clinical characteristics of aromatic L-amino acid decarboxylase deficiency in mainland China.

Wen Y, Wang J, Zhang Q, Chen Y, Bao X.

J Hum Genet. 2020 Sep;65(9):759-769. doi: 10.1038/s10038-020-0770-6. Epub 2020 May 14.

PubMed [citation]

PMID:: 32409695
PMCID:: PMC7387242

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003223952.2

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

Description

This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 447 of the DDC protein (p.Arg447Ser). 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.Arg447 amino acid residue in DDC. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 17240182, 32409695). 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This variant has not been reported in the literature in individuals affected with DDC-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%).

#	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: Jan 13, 2025

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