Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genomic Research Center, |
RCV000784921 | SCV000923462 | uncertain significance | Classic dopamine transporter deficiency syndrome | 2019-01-01 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001221916 | SCV001393987 | uncertain significance | Parkinsonism-dystonia, infantile | 2021-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine with methionine at codon 356 of the SLC6A3 protein (p.Thr356Met). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is present in population databases (rs577802449, ExAC 0.01%). This missense change has been observed in individual(s) with autism spectrum disorder (PMID: 22495311, 23979605). ClinVar contains an entry for this variant (Variation ID: 634445). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects SLC6A3 function (PMID: 23979605, 25741436, 29559554). 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. |