Submissions for variant NM_001165963.4(SCN1A):c.4573C>T (p.Arg1525Ter)

dbSNP: rs794726752

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Bioinformatics, Peking University	RCV000180863	SCV000221828	pathogenic	Severe myoclonic epilepsy in infancy	2014-12-20	criteria provided, single submitter	research
GeneDx	RCV000188962	SCV000242593	pathogenic	not provided	2016-06-29	criteria provided, single submitter	clinical testing	The Arg1525Stop variant in the SCN1A gene has been reported in several individuals with SCN1A-related disorders (Kearney et al., 2006; Harkin et al., 2007). This variant is predicted to cause loss of normal protein function through protein truncation or nonsense-mediated mRNA decay. This variant has been seen apparently mosaic.
Invitae	RCV001382664	SCV001581559	pathogenic	Early infantile epileptic encephalopathy with suppression bursts	2023-11-13	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg1525*) 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). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with SCN1A-related conditions (PMID: 16458823, 27465585, 28079314). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 189911). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
DASA	RCV002221506	SCV002499419	pathogenic	Migraine, familial hemiplegic, 3	2022-04-10	criteria provided, single submitter	clinical testing	The c.4573C>T;p.(Arg1525*) variant creates a premature translational stop signal in the SCN1A gene. It is expected to result in an absent or disrupted protein product -PVS1. This sequence change has been observed in affected individual(s) and ClinVar contains an entry for this variant (Clinvar ID: 189911; PMID: 28079314; 27465585; 17347258; 16458823) - PS4. This variant is not present in population databases (rs794726752- gnomAD; ABraOM no frequency - http://abraom.ib.usp.br) - PM2. The variant was assumed de novo, but without confirmation of paternity and maternity (PMID: 27465585) - PM6. In summary, the currently available evidence indicates that the variant is pathogenic.
Athena Diagnostics Inc	RCV000188962	SCV004230006	pathogenic	not provided	2023-03-31	criteria provided, single submitter	clinical testing	This variant is expected to result in the loss of a functional protein. This variant has been identified in multiple unrelated individuals with Dravet syndrome and severe myoclonic epilepsy of infancy (SMEI) and has been confirmed to occur de novo in multiple individuals. This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org).
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000188962	SCV001809042	pathogenic	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000188962	SCV001929100	pathogenic	not provided		no assertion criteria provided	clinical testing