Submissions for variant NM_020822.3(KCNT1):c.1066C>T (p.Arg356Trp)

dbSNP: rs752514808

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000420451	SCV000531989	pathogenic	not provided	2022-11-17	criteria provided, single submitter	clinical testing	Reported in a patient in published literature with infantile seizures who also harbored another variant in the KCNT1 gene, although familial segregation information was not provided to determine if either variant occurred de novo or to determine if the variants occurred on the same (in cis) or on different (in trans) chromosomes (Passey et al., 2019); Not observed 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: 31532594, 31216405, 31388363, 31618474, 32776321, 25326635, 34074526)
Baylor Genetics	RCV000795380	SCV000807325	pathogenic	Developmental and epileptic encephalopathy, 14; Autosomal dominant nocturnal frontal lobe epilepsy 5	2017-12-31	criteria provided, single submitter	clinical testing
Invitae	RCV000795380	SCV000934843	pathogenic	Developmental and epileptic encephalopathy, 14; Autosomal dominant nocturnal frontal lobe epilepsy 5	2022-07-26	criteria provided, single submitter	clinical testing	Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 389450). This missense change has been observed in individual(s) with KCNT1-related conditions (PMID: 25326635, 31532594; 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 arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 356 of the KCNT1 protein (p.Arg356Trp).
CeGaT Center for Human Genetics Tuebingen	RCV000420451	SCV001155834	likely pathogenic	not provided	2018-11-01	criteria provided, single submitter	clinical testing
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	RCV002252125	SCV002523408	likely pathogenic	See cases	2019-03-08	criteria provided, single submitter	clinical testing	ACMG classification criteria: PS2, PM2, PP3