Submissions for variant NM_020822.3(KCNT1):c.1967G>A (p.Gly656Asp)

gnomAD frequency: 0.00001  dbSNP: rs775458154

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CeGaT Center for Human Genetics Tuebingen	RCV000513604	SCV000609367	uncertain significance	not provided	2017-04-30	criteria provided, single submitter	clinical testing
Invitae	RCV001324564	SCV001515521	uncertain significance	Developmental and epileptic encephalopathy, 14; Autosomal dominant nocturnal frontal lobe epilepsy 5	2024-01-04	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 656 of the KCNT1 protein (p.Gly656Asp). This variant is present in population databases (rs775458154, gnomAD 0.005%). 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: 444789). 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.
Genome-Nilou Lab	RCV002270607	SCV002554772	uncertain significance	Developmental and epileptic encephalopathy, 14	2022-03-15	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002270608	SCV002554773	uncertain significance	Autosomal dominant nocturnal frontal lobe epilepsy 5	2022-03-15	criteria provided, single submitter	clinical testing