ClinVar Miner

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

gnomAD frequency: 0.00001  dbSNP: rs886062374
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000279143 SCV002259654 pathogenic Deficiency of aromatic-L-amino-acid decarboxylase 2024-05-20 criteria provided, single submitter clinical testing 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). This variant is not present in population databases (gnomAD no frequency). 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. ClinVar contains an entry for this variant (Variation ID: 360437). 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 with a positive predictive value of 80%. Experimental studies have shown that this missense change affects DDC function (PMID: 29356298). 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. For these reasons, this variant has been classified as Pathogenic.

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