ClinVar Miner

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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