Submissions for variant NM_020822.3(KCNT1):c.1726G>A (p.Glu576Lys)

gnomAD frequency: 0.00044  dbSNP: rs147306623

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000724878	SCV000226671	uncertain significance	not provided	2017-03-14	criteria provided, single submitter	clinical testing
GeneDx	RCV000724878	SCV000523050	benign	not provided	2020-09-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002312712	SCV000846788	likely benign	Inborn genetic diseases	2024-03-27	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001081967	SCV001003603	likely benign	Developmental and epileptic encephalopathy, 14; Autosomal dominant nocturnal frontal lobe epilepsy 5	2024-12-24	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000724878	SCV003812033	uncertain significance	not provided	2021-05-19	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004700536	SCV005203090	uncertain significance	not specified	2024-07-09	criteria provided, single submitter	clinical testing	Variant summary: KCNT1 c.1726G>A (p.Glu576Lys) results in a conservative amino acid change located in the Calcium-activated potassium channel BK, alpha subunit (IPR003929) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00011 in 250560 control chromosomes (gnomAD). This frequency is not significantly higher than estimated for a pathogenic variant in KCNT1 causing Developmental And Epileptic Encephalopathy, 14, allowing no conclusion about variant significance. To our knowledge, no occurrence of c.1726G>A in individuals affected with Developmental And Epileptic Encephalopathy, 14 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 194781). Based on the evidence outlined above, the variant was classified as uncertain significance.
PreventionGenetics, part of Exact Sciences	RCV003947481	SCV004763894	likely benign	KCNT1-related disorder	2023-06-06	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).