Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000489904 | SCV000577156 | likely pathogenic | not provided | 2021-03-08 | criteria provided, single submitter | clinical testing | In-silico analysis, which includes splice predictors and evolutionary conservation, is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 19350499, 29408779) |
Greenwood Genetic Center Diagnostic Laboratories, |
RCV001814163 | SCV002061418 | likely pathogenic | Severe myoclonic epilepsy in infancy; Developmental and epileptic encephalopathy 6B | 2021-06-15 | criteria provided, single submitter | clinical testing | PS2, PS4_Supporting, PM2 |
Invitae | RCV002526025 | SCV003525063 | likely pathogenic | Early infantile epileptic encephalopathy with suppression bursts | 2022-04-22 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 426654). This variant is also known as K1492K. This variant has been observed in individual(s) with severe myoclonic epilepsy of infancy (PMID: 19350499). 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 codon 1492 of the SCN1A mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the SCN1A protein. This variant also falls at the last nucleotide of exon 23, which is part of the consensus splice site for this exon. Variants that disrupt 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. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
Athena Diagnostics Inc | RCV000489904 | SCV004230003 | pathogenic | not provided | 2023-07-05 | criteria provided, single submitter | clinical testing | This variant has been confirmed to occur de novo in multiple individuals with Dravet syndrome. This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). |