Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000810423 | SCV000950621 | pathogenic | Early infantile epileptic encephalopathy with suppression bursts | 2024-01-02 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1350 of the SCN1A protein (p.Val1350Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with febrile seizures (Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 654455). 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 with a positive predictive value of 95%. This variant disrupts the p.Val1350 amino acid residue in SCN1A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 21248271). 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. |