Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003596499 | SCV000817752 | likely pathogenic | Myoclonic-atonic epilepsy | 2018-06-06 | criteria provided, single submitter | clinical testing | This variant has been observed to be de novo in individuals affected with refractory generalized seizures (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces methionine with threonine at codon 487 of the SLC6A1 protein (p.Met487Thr). The methionine residue is highly conserved and there is a moderate physicochemical difference between methionine and threonine. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |