Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001339387 | SCV001533127 | pathogenic | Early infantile epileptic encephalopathy with suppression bursts | 2023-03-04 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the Val1630 amino acid residue in SCN1A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 23195492). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SCN1A protein function. ClinVar contains an entry for this variant (Variation ID: 68556). This missense change has been observed in individual(s) with Dravet syndrome (PMID: 17561957). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 1630 of the SCN1A protein (p.Val1630Met). |
| New York Genome Center | RCV001781396 | SCV002025661 | uncertain significance | Severe myoclonic epilepsy in infancy; Generalized epilepsy with febrile seizures plus, type 2 | 2020-04-25 | criteria provided, single submitter | clinical testing | The p.Val1630Met variant in SCN1A has been reported in a patient affected with familial severe myoclonic epilepsy of infancy [PMID: 17561957]. Patient’s EEG results showed generalized spike-wave & multifocal [supplemental table 3 of www.ncbi.nlm.nih.gov/books/NBK1318/]. The p.Val1630Met variant is absent from the gnomAD database indicating it is an extremely rare allele. The variant affects an evolutionarily conserved residue located in the D4/S3-S4ex extracellular region of the SCN1A protein [PMID: 18804930] and is predicted deleterious by multiple in silico prediction tools. Two different missense variants affecting the same p.Val1630 residue (p.Val1630Glyand p.Val1630Leu) have been reported in individuals affected with SCN1A-associated disorders [PMID: 27465585; PMID: 23195492; PMID: 22092154]. However, functional studies have not been performed to evaluate the potential pathogenicity of variants affecting the residue p.V1630 of SCN1A. Based on the available evidence, the p.Val1630Met variant is assessed as a variant of uncertain significance suspicious of likely pathogenic. |
| Uni |
RCV000059430 | SCV000090954 | not provided | Severe myoclonic epilepsy in infancy | no assertion provided | not provided |