Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001366716 | SCV001563029 | pathogenic | Deficiency of aromatic-L-amino-acid decarboxylase | 2023-12-01 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 69 of the DDC protein (p.Thr69Met). This variant is present in population databases (rs777956037, gnomAD 0.01%). This missense change has been observed in individual(s) with aromatic L-amino acid decarboxylase deficiency (PMID: 20505134, 31849064). ClinVar contains an entry for this variant (Variation ID: 1057684). 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 are conflicting or provide insufficient evidence to determine the effect of this variant on DDC function (PMID: 24865461). For these reasons, this variant has been classified as Pathogenic. |
| Revvity Omics, |
RCV001366716 | SCV003834299 | uncertain significance | Deficiency of aromatic-L-amino-acid decarboxylase | 2019-12-16 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001366716 | SCV005076293 | pathogenic | Deficiency of aromatic-L-amino-acid decarboxylase | 2024-04-12 | criteria provided, single submitter | clinical testing | Variant summary: DDC c.206C>T (p.Thr69Met) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.6e-05 in 248168 control chromosomes. c.206C>T has been reported in the literature in multiple homozygous and compound heterozygous individuals affected with Deficiency Of Aromatic-L-Amino-Acid Decarboxylase (e.g. Brennenstuhl_2020, Yubero_2016, Manegold_2009, Pearson_2020, Abukhaled_2023). These data indicate that the variant is likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in enzyme activity <10% of normal activity in vitro (e.g. Manegold_2009). The following publications have been ascertained in the context of this evaluation (PMID: 36727005, 32675002, 19172410, 31130284, 32369189, 27243974). ClinVar contains an entry for this variant (Variation ID: 1057684). Based on the evidence outlined above, the variant was classified as pathogenic. |
| Center for Genomic Medicine, |
RCV001366716 | SCV005374344 | pathogenic | Deficiency of aromatic-L-amino-acid decarboxylase | 2024-09-22 | criteria provided, single submitter | clinical testing |