ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.5674C>T (p.Arg1892Ter) (rs794726739)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Bioinformatics, Peking University RCV000180848 SCV000221813 pathogenic Severe myoclonic epilepsy in infancy 2014-12-20 criteria provided, single submitter research
GeneDx RCV000189004 SCV000242635 pathogenic not provided 2014-03-13 criteria provided, single submitter clinical testing p.Arg1892Stop (CGA>TGA): c.5674 C>T in exon 26 of the SCN1A gene (NM_001165963.1) The R1892X nonsense mutation in the SCN1A gene has been reported in multiple unrelated patients with Dravet syndrome and other SCN1A-related disorders (Sugawara et al., 2002). This mutation is predicted to cause loss of normal protein function through protein truncation. The variant is found in EPILEPSY panel(s).
Invitae RCV000805798 SCV000945767 pathogenic Early infantile epileptic encephalopathy with suppression bursts 2018-10-31 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the SCN1A gene (p.Arg1892*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 118 amino acids of the SCN1A protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in several individuals affected with severe myoclonic epilepsy of infancy (SMEI) (PMID: 17054684) and has also been observed in several individuals with clinical features of SMEI (PMID: 11940708, 19563349). It is also known as c.5641C>T: Arg1881X in the literature. ClinVar contains an entry for this variant (Variation ID: 189896). This variant disrupts the C-terminus of the SCN1A protein. Other variant(s) that disrupt this region (p.Arg1924Leufs*8) have been determined to be pathogenic (PMID: 27465585). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000189004 SCV001245861 pathogenic not provided 2019-07-01 criteria provided, single submitter clinical testing
Institute of Human Genetics, Klinikum rechts der Isar RCV000995637 SCV001149920 pathogenic Generalized epilepsy with febrile seizures plus, type 2 2019-09-30 no assertion criteria provided clinical testing

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