ClinVar Miner

Submissions for variant NM_001082971.2(DDC):c.478C>T (p.Arg160Trp)

dbSNP: rs886062374
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000279143 SCV000469601 uncertain significance Deficiency of aromatic-L-amino-acid decarboxylase 2017-04-28 criteria provided, single submitter clinical testing The DDC c.478C>T (p.Arg160Trp) variant is a missense variant that has been identified in a compound heterozygote state with a second missense variant in one individual with aromatic L-amino acid decarboxylase deficiency (Barth et al. 2011). The AADC enzymatic activity in the patient was 8% of the mean of the child reference range, confirming AADC enzyme deficiency. Control data are unavailable for the p.Arg160Trp variant, and it 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. The variant is thus presumed to be rare. The evidence for this variant is limited. The p.Arg160Trp variant is therefore 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 RCV000279143 SCV002259654 likely pathogenic Deficiency of aromatic-L-amino-acid decarboxylase 2022-01-31 criteria provided, single submitter clinical testing In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Arg160 amino acid residue in DDC. Other variant(s) that disrupt this residue have been observed in individuals with DDC-related conditions (PMID: 31975548), which suggests that this may be a clinically significant amino acid residue. Experimental studies have shown that this missense change affects DDC function (PMID: 29356298). 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. ClinVar contains an entry for this variant (Variation ID: 360437). This missense change has been observed in individual(s) with aromatic L-amino acid decarboxylase deficiency (PMID: 23430870). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 160 of the DDC protein (p.Arg160Trp).

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