Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000560438 | SCV000637343 | uncertain significance | Torsion dystonia 6 | 2016-08-03 | criteria provided, single submitter | clinical testing | In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a THAP1-related disease.  However, two different substitutions of this amino acid (p.Cys54Phe and p.Cys54Tyr) have been reported in individuals with dystonia (PMIDs: 21800139, 20865765). This sequence change replaces cysteine with serine at codon 54 of the THAP1 protein (p.Cys54Ser). The cysteine residue is highly conserved and there is a moderate physicochemical difference between cysteine and serine. |