Submissions for variant NM_001040142.2(SCN2A):c.4303C>T (p.Arg1435Ter) (rs796053138)

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Total submissions: 4

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000485232	SCV000567713	pathogenic	not provided	2015-09-01	criteria provided, single submitter	clinical testing	The R1435X nonsense variant in the SCN2A gene has not been reported previously as a pathogenic variant nor as a benign polymorphism, to our knowledge. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R1435X variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret R1435X as a pathogenic variant.
NeuroMeGen,Hospital Clinico Santiago de Compostela	RCV000585884	SCV000693773	likely pathogenic	Early infantile epileptic encephalopathy 11	2018-01-01	criteria provided, single submitter	clinical testing
Invitae	RCV000640630	SCV000762224	pathogenic	Benign familial neonatal-infantile seizures; Early infantile epileptic encephalopathy 11	2018-11-08	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg1435*) in the SCN2A gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported to be de novo in individuals affected with autism spectrum disorders, severe intellectual disability, and/or seizures (PMID: 26993267, 28379373). ClinVar contains an entry for this variant (Variation ID: 419721). Loss-of-function variants in SCN2A are known to be pathogenic (PMID: 2635020, 22495306, 23020937, 24650168). For these reasons, this variant has been classified as Pathogenic.
Equipe Genetique des Anomalies du Developpement,Université de Bourgogne	RCV000585884	SCV000803822	likely pathogenic	Early infantile epileptic encephalopathy 11	2017-09-13	criteria provided, single submitter	clinical testing

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