ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.383+1A>G (rs794726803)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Bioinformatics, Peking University RCV000180921 SCV000221898 pathogenic Severe myoclonic epilepsy in infancy 2014-12-20 criteria provided, single submitter research
Ambry Genetics RCV000720919 SCV000851803 pathogenic History of neurodevelopmental disorder 2017-07-03 criteria provided, single submitter clinical testing The c.383+1A>G intronic pathogenic mutation results from an A to G substitution one nucleotide after coding exon 2 of the SCN1A gene. This mutation has been detected as de novo occurrences in two unrelated individuals fulfilling diagnostic criteria for Dravet syndrome and Lennox-Gastaut syndrome (LGS); however paternity was not confirmed in either case (Selmer KK, et al.Epilepsy Behav 2009; 16(3):555-7. Xu X, et al.Brain Dev. 2014; 36(8):676-81). A similar alteration, located at the same nucleotide position, c.383+1A>C, was detected in an individual fulfilling diagnostic criteria for Dravet syndrome (Depienne C, et al. J. Med. Genet. 2009; 46(3):183-91). Based on the supporting evidence,c.383+1A>Gis interpreted as a disease-causing mutation.
Invitae RCV000824285 SCV000965178 pathogenic Early infantile epileptic encephalopathy with suppression bursts 2018-09-11 criteria provided, single submitter clinical testing This sequence change falls in intron 2 of the SCN1A gene. It does not directly change the encoded amino acid sequence of the SCN1A protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with early infantile epileptic encephalopathy or Dravet syndrome, in some of whom it was found de novo (PMID: 23884151, 19782004, Invitae). ClinVar contains an entry for this variant (Variation ID: 189967). A different variant affecting this nucleotide (c.383+1A>C) has been determined to be pathogenic (PMID: 18930999). This suggests that this nucleotide is important for normal RNA splicing, and that other variants at this position may also be pathogenic. For these reasons, this variant has been classified as Pathogenic.

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