Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001346720 | SCV001540944 | uncertain significance | Developmental and epileptic encephalopathy, 14; Autosomal dominant nocturnal frontal lobe epilepsy 5 | 2023-12-11 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 1149 of the KCNT1 protein (p.Leu1149Phe). This variant is present in population databases (no rsID available, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with KCNT1-related conditions. This missense change has been observed in at least one individual who was not affected with KCNT1-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 1042722). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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. |
Ambry Genetics | RCV002547456 | SCV003564739 | uncertain significance | Inborn genetic diseases | 2021-03-31 | criteria provided, single submitter | clinical testing | The c.3445C>T (p.L1149F) alteration is located in exon 29 (coding exon 29) of the KCNT1 gene. This alteration results from a C to T substitution at nucleotide position 3445, causing the leucine (L) at amino acid position 1149 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |