ClinVar Miner

Submissions for variant NM_020822.3(KCNT1):c.136C>T (p.Leu46Phe)

dbSNP: rs869312682
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology RCV000209840 SCV000265546 likely benign Developmental and epileptic encephalopathy, 14 2018-04-16 criteria provided, single submitter research
Invitae RCV000687849 SCV000815438 uncertain significance Developmental and epileptic encephalopathy, 14; Autosomal dominant nocturnal frontal lobe epilepsy 5 2023-11-02 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 46 of the KCNT1 protein (p.Leu46Phe). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with intellectual disability, autism spectrum disorder, speech delay, and seizures (PMID: 28554332). ClinVar contains an entry for this variant (Variation ID: 224110). 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 with a negative predictive value of 95%. 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.

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