Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001390614 | SCV001592403 | pathogenic | Early infantile epileptic encephalopathy with suppression bursts | 2023-12-14 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 343 of the SCN1A protein (p.Gly343Asp). This variant also falls at the last nucleotide of exon 7, which is part of the consensus splice site for this exon. This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with SCN1A-related conditions (PMID: 12566275, 35074891). ClinVar contains an entry for this variant (Variation ID: 68585). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). This variant disrupts the p.Gly343 amino acid residue in SCN1A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 28012175). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV002381374 | SCV002690328 | likely pathogenic | Inborn genetic diseases | 2017-12-26 | criteria provided, single submitter | clinical testing | The c.1028G>A variant (also known as p.G343D), located in coding exon 7 of the SCN1A gene, results from a G to A substitution at nucleotide position 1028. The amino acid change results in glycine to aspartic acid at codon 343, an amino acid with similar properties. However, this change occurs in the last base pair of coding exon 7, which makes it likely to have some effect on normal mRNA splicing. This alteration has been detected in an individual with a typical Dravet syndrome phenotype, including weekly generalized tonic clonic (GTCS) and complex partial (CPS) seizures, severe intellectual disability, and ataxic gait (Takayama R et al. Epilepsia, 2014 Apr;55:528-38). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| Uni |
RCV000059461 | SCV000090986 | not provided | Severe myoclonic epilepsy in infancy | no assertion provided | not provided |