Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001221069 | SCV001393092 | uncertain significance | Developmental and epileptic encephalopathy, 14; Autosomal dominant nocturnal frontal lobe epilepsy 5 | 2022-11-11 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 949580). This variant has not been reported in the literature in individuals affected with KCNT1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.004%). This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 449 of the KCNT1 protein (p.Asn449Ser). |
New York Genome Center | RCV002275313 | SCV002564226 | uncertain significance | Developmental and epileptic encephalopathy, 14 | 2021-10-01 | criteria provided, single submitter | clinical testing | The missense variant c.1346A>G, p.Asn449Ser identified in the KCNT1 gene has not been reported in individuals with KCNT1-related disorder. This variant has one heterozygous individual in gnomAD v3.1.1 suggesting it is not a common benign variant in the populations represented in this database. In silico algorithms predict a conflicting effect of pathogenicity. Based on the available evidence, the missense variant c.1346A>G, p.Asn449Ser in the KCNT1 gene is classified as a variant of uncertain significance. |