Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001698287 | SCV000532423 | likely benign | not provided | 2021-02-09 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 31875159) |
Invitae | RCV000650625 | SCV000772472 | uncertain significance | Developmental and epileptic encephalopathy, 14; Autosomal dominant nocturnal frontal lobe epilepsy 5 | 2023-10-16 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 892 of the KCNT1 protein (p.Glu892Lys). This variant is present in population databases (rs376757326, gnomAD 0.03%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with focal epilepsy (PMID: 31875159). ClinVar contains an entry for this variant (Variation ID: 389773). 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 not expected to disrupt KCNT1 protein function. 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. |
Center for Genomics, |
RCV000650625 | SCV003920112 | uncertain significance | Developmental and epileptic encephalopathy, 14; Autosomal dominant nocturnal frontal lobe epilepsy 5 | 2022-08-18 | criteria provided, single submitter | clinical testing | This variant has been reported in the literature in 1 individual with focal epilepsy (Kang 2019 PMID:31875159). This variant is present in the Genome Aggregation Database (Highest reported MAF 0.009% (4/41414) (https://gnomad.broadinstitute.org/variant/9-135778767-G-A?dataset=gnomad_r3). This variant is present in ClinVar (Variation ID:389773). This variant amino acid Lysine (Lys) is present in 2 mammal species but is otherwise highly conserved. Additional computational prediction tools for this variant are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. |
Prevention |
RCV003409605 | SCV004116263 | uncertain significance | KCNT1-related disorder | 2023-09-18 | criteria provided, single submitter | clinical testing | The KCNT1 c.2674G>A variant is predicted to result in the amino acid substitution p.Glu892Lys. This variant was reported in an individual with focal epilepsy (Table S2, Kang et al. 2019. PubMed ID: 31875159). This variant is reported in 0.035% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/9-138670613-G-A). While we suspect this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |