Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001229030 | SCV001401461 | pathogenic | Early infantile epileptic encephalopathy with suppression bursts | 2019-09-17 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in intron 18 of the SCN1A gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. Disruption of this splice site has been observed in individual(s) with severe myoclonic epilepsy of infancy (PMID: 17054684). In at least one individual the variant was observed to be de novo. For these reasons, this variant has been classified as Pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in SCN1A are known to be pathogenic (PMID: 17347258, 18930999). 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. |