Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000422915 | SCV000535078 | uncertain significance | not provided | 2017-01-06 | criteria provided, single submitter | clinical testing | The D298H variant in the TH gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The D298H variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The D298H variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret D298H as a variant of uncertain significance. |
| Labcorp Genetics |
RCV001271313 | SCV002294587 | uncertain significance | Autosomal recessive DOPA responsive dystonia | 2023-11-27 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 298 of the TH protein (p.Asp298His). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TH-related conditions. ClinVar contains an entry for this variant (Variation ID: 391909). 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 TH protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Natera, |
RCV001271313 | SCV001452395 | uncertain significance | Autosomal recessive DOPA responsive dystonia | 2020-03-17 | no assertion criteria provided | clinical testing |