Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002036798 | SCV002317929 | likely pathogenic | Developmental and epileptic encephalopathy, 14; Autosomal dominant nocturnal frontal lobe epilepsy 5 | 2020-10-29 | criteria provided, single submitter | clinical testing | 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. This variant disrupts the p.Ala934 amino acid residue in KCNT1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 23086397, 26140313, 26993267). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt KCNT1 protein function. This variant has been observed in individual(s) with clinical features of autosomal dominant nocturnal frontal lobe epilepsy (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with serine at codon 934 of the KCNT1 protein (p.Ala934Ser). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and serine. |
| Génétique des Maladies du Développement, |
RCV002280205 | SCV002568455 | pathogenic | Seizure | 2022-08-30 | no assertion criteria provided | clinical testing |