Submissions for variant NM_020822.3(KCNT1):c.3685A>G (p.Thr1229Ala)

gnomAD frequency: 0.00057  dbSNP: rs74533482

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000514013	SCV000513389	benign	not provided	2018-04-24	criteria provided, single submitter	clinical testing
Invitae	RCV001085417	SCV000553817	likely benign	Developmental and epileptic encephalopathy, 14; Autosomal dominant nocturnal frontal lobe epilepsy 5	2024-01-19	criteria provided, single submitter	clinical testing
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000514013	SCV000609955	likely benign	not provided	2017-05-11	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002314149	SCV000848081	likely benign	Inborn genetic diseases	2018-09-15	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.
Genome-Nilou Lab	RCV002270253	SCV002553738	benign	Developmental and epileptic encephalopathy, 14	2022-03-15	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002270254	SCV002553739	benign	Autosomal dominant nocturnal frontal lobe epilepsy 5	2022-03-15	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000514013	SCV002585102	likely benign	not provided	2023-07-01	criteria provided, single submitter	clinical testing	KCNT1: BP4, BS1
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV001085417	SCV003924120	likely benign	Developmental and epileptic encephalopathy, 14; Autosomal dominant nocturnal frontal lobe epilepsy 5	2021-03-30	criteria provided, single submitter	clinical testing	KCNT1 NM_020822.2 exon 31 p.Thr1229Ala (c.3685A>G): This variant has not been reported in the literature but is present in 0.1% (72/64504) of European alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/9-135792138-A-G?dataset=gnomad_r3). This variant is present in ClinVar, with several labs classifying this variant as likely benign (Variation ID: 378038). Evolutionary conservation for this variant is unclear; computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant suggests that this variant does not cause disease, but requires further evidence. Therefore this variant is classified as likely benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000514013	SCV004564638	likely benign	not provided	2023-10-09	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003912620	SCV004731789	likely benign	KCNT1-related disorder	2022-02-16	criteria provided, single submitter	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).