Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Mendelics | RCV000986892 | SCV001136042 | likely pathogenic | Severe myoclonic epilepsy in infancy | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001593162 | SCV001824468 | pathogenic | not provided | 2020-04-03 | criteria provided, single submitter | clinical testing | Reported previously in an individual with Dravet syndrome, however parental studies were not performed (Zuberi et al., 2011); Canonical splice site variant in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 32090326, 21248271, 29408779, 25525159, 29655203) |
Invitae | RCV002549674 | SCV003524846 | pathogenic | Early infantile epileptic encephalopathy with suppression bursts | 2021-08-31 | 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: 801801). Disruption of this splice site has been observed in individual(s) with Dravet syndrome and/or SCN1A-related conditions (PMID: 21248271; Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 16 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). |
Neuberg Supratech Reference Laboratories Pvt Ltd, |
RCV000986892 | SCV004047720 | likely pathogenic | Severe myoclonic epilepsy in infancy | criteria provided, single submitter | clinical testing | The invariant splice site c.3429+1G>T has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.3429+1G>T variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. This variant has been reported to the ClinVar database as Pathogenic/Likely Pathogenic. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Likely Pathogenic |