ClinVar Miner

Submissions for variant NM_001082971.2(DDC):c.272C>T (p.Ala91Val)

gnomAD frequency: 0.00004  dbSNP: rs137853211
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000019391 SCV001574685 pathogenic Deficiency of aromatic-L-amino-acid decarboxylase 2023-10-10 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 91 of the DDC protein (p.Ala91Val). This variant is present in population databases (rs137853211, gnomAD 0.009%). This missense change has been observed in individual(s) with aromatic L-amino acid decarboxylase deficiency (PMID: 9789536, 30952622, 31104889; Invitae). ClinVar contains an entry for this variant (Variation ID: 17813). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on DDC protein function. Experimental studies have shown that this missense change affects DDC function (PMID: 31104889). For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity RCV000019391 SCV003834298 uncertain significance Deficiency of aromatic-L-amino-acid decarboxylase 2019-12-16 criteria provided, single submitter clinical testing
GeneDx RCV003238725 SCV003936444 likely pathogenic not provided 2023-06-01 criteria provided, single submitter clinical testing Published functional studies demonstrate that the variant affects enzyme activity in vitro (Montioli et al., 2019); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Reported previously with one or more other variants in DDC in individuals with aromatic L-amino acid decarboxylase (AADC) deficiency (Wassenberg et al., 2010; Montiolo et al., 2019; Gantz et al., 2023); This variant is associated with the following publications: (PMID: 9789536, 36232540, 36427457, 30952622, Gantz2023 [CaseReport], 36096017, 33808712, 31104889, 20832343)
OMIM RCV000019391 SCV000039681 pathogenic Deficiency of aromatic-L-amino-acid decarboxylase 2022-08-11 no assertion criteria provided literature only

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