Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Baylor Genetics | RCV001328665 | SCV001519833 | pathogenic | Severe myoclonic epilepsy in infancy | 2020-05-05 | criteria provided, single submitter | clinical testing | This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. |
Invitae | RCV003753174 | SCV004461179 | pathogenic | Early infantile epileptic encephalopathy with suppression bursts | 2023-05-01 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 1027785). 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. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 10 of the SCN1A gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site 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). |