ClinVar Miner

Submissions for variant NM_020822.3(KCNT1):c.1783C>T (p.Leu595Phe)

gnomAD frequency: 0.00004  dbSNP: rs950983477
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001206171 SCV001377467 uncertain significance Developmental and epileptic encephalopathy, 14; Autosomal dominant nocturnal frontal lobe epilepsy 5 2023-03-30 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 expected to disrupt KCNT1 protein function. ClinVar contains an entry for this variant (Variation ID: 937205). 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 0.02%). This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 595 of the KCNT1 protein (p.Leu595Phe).
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV001206171 SCV003920108 uncertain significance Developmental and epileptic encephalopathy, 14; Autosomal dominant nocturnal frontal lobe epilepsy 5 2021-03-30 criteria provided, single submitter clinical testing KCNT1 NM_020822.2 exon 18 p.Leu595Phe (c.1783C>T): This variant has not been reported in the literature but is present in 3/18742 African alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.

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