Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002232079 | SCV000648424 | uncertain significance | Parkinsonism-dystonia, infantile | 2021-04-30 | criteria provided, single submitter | clinical testing | Experimental studies have shown that this missense change leads to altered protein function and localization in cell culture experiments (PMID: 22514303, 25747272). In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. This variant has been reported in individuals affected with attention-deficit hyperactivity disorder (ADHD). This variant is also described as 2026T/C in the literature. In the same study the authors incorrectly refer to this variant in the SLC6A4 gene, while later describing it correctly as being present in the SLC6A3 gene (PMID: 22514303). This sequence change replaces arginine with cysteine at codon 615 of the SLC6A3 protein (p.Arg615Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases at a very low frequency (rs763131939, ExAC <0.01%). |