ClinVar Miner

Submissions for variant NM_001082971.2(DDC):c.853C>T (p.Arg285Trp)

gnomAD frequency: 0.00001  dbSNP: rs886062372
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000334201 SCV000469596 uncertain significance Deficiency of aromatic-L-amino-acid decarboxylase 2017-04-28 criteria provided, single submitter clinical testing The DDC c.853C>T (p.Arg285Trp) variant is a missense variant that has been reported in one study, in which it was found in a compound heterozygous state with an intron variant in two siblings with a mild aromatic l-amino acid decarboxylase deficiency phenotype (Tay et al. 2007). The p.Arg285Trp variant was absent from 100 controls and is not found in the 1000 Genomes Project, the Exome Sequencing Project, or the Exome Aggregation Consortium despite being located in a region of good sequencing coverage, suggesting it is rare. Montioli et al. (2014) demonstrated that the p.Arg285Trp variant protein was expressed at levels of 50-70% compared to wildtype and exhibited abnormal kinetics, including a reduced kcat value compared to wildtype. Based on the evidence, the p.Arg285Trp variant is classified as a variant of unknown significance but suspicious for pathogenicity for aromatic l-amino acid decarboxylase deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV000334201 SCV003440237 pathogenic Deficiency of aromatic-L-amino-acid decarboxylase 2022-10-04 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Experimental studies have shown that this missense change affects DDC function (PMID: 24865461). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt DDC protein function. ClinVar contains an entry for this variant (Variation ID: 360433). This missense change has been observed in individual(s) with aromatic L-amino acid decarboxylase deficiency (PMID: 17533144). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is present in population databases (no rsID available, gnomAD 0.06%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 285 of the DDC protein (p.Arg285Trp).
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center RCV000334201 SCV004806263 uncertain significance Deficiency of aromatic-L-amino-acid decarboxylase 2024-03-25 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.