Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000812238 | SCV000952545 | pathogenic | Developmental and epileptic encephalopathy, 14; Autosomal dominant nocturnal frontal lobe epilepsy 5 | 2019-07-15 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Gln906 amino acid residue in KCNT1. Other variant(s) that disrupt this residue have been observed in affected individuals (PMID: 26597493), which suggests that this may be a clinically significant amino acid residue. 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed to be de novo in an individual with clinical features of early infantile epileptic encephalopathy (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamine with arginine at codon 906 of the KCNT1 protein (p.Gln906Arg). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and arginine. |
| Center of Excellence for Medical Genomics, |
RCV002281580 | SCV002570032 | pathogenic | Autosomal dominant nocturnal frontal lobe epilepsy 5 | 2002-09-08 | no assertion criteria provided | research |