Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002318003 | SCV000849581 | uncertain significance | Inborn genetic diseases | 2017-05-11 | criteria provided, single submitter | clinical testing | The p.R613Q variant (also known as c.1838G>A), located in coding exon 18 of the KCNT1 gene, results from a G to A substitution at nucleotide position 1838. The arginine at codon 613 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV001037669 | SCV001201093 | uncertain significance | Developmental and epileptic encephalopathy, 14; Autosomal dominant nocturnal frontal lobe epilepsy 5 | 2024-01-15 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 613 of the KCNT1 protein (p.Arg613Gln). This variant is present in population databases (rs571757257, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with KCNT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 589059). 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 80%. 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. |
| Gene |
RCV001585675 | SCV001813987 | likely benign | not provided | 2018-11-12 | criteria provided, single submitter | clinical testing | |
| New York Genome Center | RCV001037669 | SCV002564175 | uncertain significance | Developmental and epileptic encephalopathy, 14; Autosomal dominant nocturnal frontal lobe epilepsy 5 | 2021-10-01 | criteria provided, single submitter | clinical testing | The inherited heterozygous missense variant c.1838G>A (p.Arg613Gln) identified in exon 18 (of 31) of the KCNT1 gene has not been reported in affected individuals in the literature. The variant has 0.00001972 allele frequency in the gnomAD(v3) database (3 out of 152144 heterozygous alleles, no homozygotes) suggesting it is not a common benign variant in the populations represented in that database. This variant is reported as a variant of uncertain significance and likely benign in the ClinVar database (Variation ID: 589059). This variant affects a highly conserved residue (Arg613) of the KCNT1 gene. In silico tools provide conflicting predictions about pathogenicity of this variant (CADD score = 24.00, REVEL score = 0.192). Reduced penetrance has been reported in KCNT1-related epilepsy phenotypes (PMID: 26122718, 30234941). Based on the available evidence, the inherited heterozygous c.1838G>A (p.Arg613Gln) missense variant identified in the KCNT1 gene is reported as a Variant of UncertainSignificance. |
| Revvity Omics, |
RCV001585675 | SCV003812016 | uncertain significance | not provided | 2022-09-20 | criteria provided, single submitter | clinical testing |