ClinVar Miner

Submissions for variant NM_006920.6(SCN1A):c.4819+1G>T (rs1573962555)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000808951 SCV000949085 pathogenic Early infantile epileptic encephalopathy 2019-01-31 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in the last intron (intron 25) of the SCN1A gene. While this is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in an individual affected with SCN1A-related disease (Invitae). A different variant that affects this splice site (c.4852+2T>C) has been observed in individuals affected with generalized epilepsy with febrile seizures plus (GEFS+) and Dravet syndrome (PMID: 28202706, 21248271). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic.

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