Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000461071 | SCV000553827 | uncertain significance | Developmental and epileptic encephalopathy, 14; Autosomal dominant nocturnal frontal lobe epilepsy 5 | 2021-03-08 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a KCNT1-related disease. 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This sequence change replaces arginine with cysteine at codon 67 of the KCNT1 protein (p.Arg67Cys). The arginine residue is weakly conserved and there is a large physicochemical difference between arginine and cysteine. |