Submissions for variant NM_001165963.4(SCN1A):c.3637C>T (p.Arg1213Ter)

dbSNP: rs794726710

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Bioinformatics, Peking University	RCV000180814	SCV000221776	pathogenic	Severe myoclonic epilepsy in infancy	2014-12-20	criteria provided, single submitter	research
GeneDx	RCV000189082	SCV000242713	pathogenic	not provided	2023-04-21	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 30368457, 32090326, 28005047, 29573403, 35571021, 31440721, 29186148, 26096185, 26232052, 35074891, 18930999, 15346159, 23934111, 12566275, 23195492)
Athena Diagnostics Inc	RCV000180814	SCV000255823	pathogenic	Severe myoclonic epilepsy in infancy	2014-06-10	criteria provided, single submitter	clinical testing
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology	RCV000180814	SCV000265529	pathogenic	Severe myoclonic epilepsy in infancy	2014-11-04	criteria provided, single submitter	research
Center of Genomic medicine, Geneva, University Hospital of Geneva	RCV000585684	SCV000693448	pathogenic	Seizure	2017-09-14	criteria provided, single submitter	clinical testing	This pathogenic mutation in the SCN1A gene was found in a child with epilepsy since the age of 5 months.
Invitae	RCV000808766	SCV000948885	pathogenic	Early infantile epileptic encephalopathy with suppression bursts	2023-05-10	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 189861). This premature translational stop signal has been observed in individual(s) with intractable epilepsy and Dravet syndrome (PMID: 12566275, 18930999, 23195492, 23934111). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg1213*) in the SCN1A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SCN1A are known to be pathogenic (PMID: 17347258, 18930999).
CeGaT Center for Human Genetics Tuebingen	RCV000189082	SCV001247846	pathogenic	not provided	2019-07-01	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	RCV000180814	SCV001428929	pathogenic	Severe myoclonic epilepsy in infancy	2017-09-05	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002453572	SCV002614186	pathogenic	Inborn genetic diseases	2018-09-21	criteria provided, single submitter	clinical testing	The p.R1213* pathogenic mutation (also known as c.3637C>T), located in coding exon 18 of the SCN1A gene, results from a C to T substitution at nucleotide position 3637. This changes the amino acid from an arginine to a stop codon within coding exon 18. This mutation has been detected in multiple patients with early onset epilepsy phenotypes including Dravet syndrome and intractable epilepsy in infancy, with some cases reported as occurring de novo (Fujiwara T et al. Brain. 2003;126:531-46; Depienne C et al. J. Med. Genet., 2009;46:183-91; Wang JW et al. Epilepsy Res. 2012;102:195-200; Allen et al. Nature. 2013;501:217-21; van Egmond ME et al. Eur. J. Paediatr. Neurol., 2015;19:726-9; Zhu X et al. PLoS Genet. 2017;13:e1007104). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Center of Excellence for Medical Genomics, Chulalongkorn University	RCV002281564	SCV002570034	pathogenic	Migraine, familial hemiplegic, 3	2002-09-08	no assertion criteria provided	research