ClinVar Miner

Submissions for variant NM_020822.3(KCNT1):c.1885A>G (p.Lys629Glu)

dbSNP: rs1057522978
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000425973 SCV000530238 pathogenic not provided 2022-10-10 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 32167590, 35363364, 27779742)
Labcorp Genetics (formerly Invitae), Labcorp RCV001383750 SCV001583005 pathogenic Developmental and epileptic encephalopathy, 14; Autosomal dominant nocturnal frontal lobe epilepsy 5 2022-08-10 criteria provided, single submitter clinical testing This variant disrupts the p.Lys629 amino acid residue in KCNT1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 26369628). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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: 388032). This missense change has been observed in individual(s) with KCNT1-related conditions (PMID: 27779742; Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 629 of the KCNT1 protein (p.Lys629Glu).
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne RCV001731682 SCV001985062 likely pathogenic Developmental and epileptic encephalopathy, 14 2021-10-18 criteria provided, single submitter clinical testing

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