Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000013122 | SCV002181162 | uncertain significance | Autosomal recessive DOPA responsive dystonia | 2022-08-09 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 276 of the TH protein (p.Thr276Pro). This variant is present in population databases (rs28934581, gnomAD 0.003%). This missense change has been observed in individual(s) with infantile parkinsonism (PMID: 11246459). This variant is also known as p.Thr276Pro. ClinVar contains an entry for this variant (Variation ID: 12329). 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 TH protein function. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on TH function (PMID: 22583432, 24753243). 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. |
OMIM | RCV000013122 | SCV000033369 | pathogenic | Autosomal recessive DOPA responsive dystonia | 2000-01-01 | no assertion criteria provided | literature only |