Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002345371 | SCV002647492 | likely pathogenic | Inborn genetic diseases | 2018-03-20 | criteria provided, single submitter | clinical testing | The p.F403L variant (also known as c.1207T>C), located in coding exon 9 of the SCN1A gene, results from a T to C substitution at nucleotide position 1207. The phenylalanine at codon 403 is replaced by leucine, an amino acid with highly similar properties. This alteration has been detected as de novo in two individuals with severe myoclonic epilepsy in infancy (SMEI) (Harkin LA et al. Brain, 2007 Mar;130:843-52; Berkovic SF et al. Lancet Neurol, 2006 Jun;5:488-92). A different alteration located at the same position, p.F403V, was detected in one individual with classic Dravet syndrome (Zuberi SM et al. Neurology, 2011 Feb;76:594-600). 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. |
| Invitae | RCV002514305 | SCV003525070 | pathogenic | Early infantile epileptic encephalopathy with suppression bursts | 2022-10-09 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. 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. This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 403 of the SCN1A protein (p.Phe403Leu). 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: 17347258). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 68508). |
| Uni |
RCV000059380 | SCV000090904 | not provided | Severe myoclonic epilepsy in infancy | no assertion provided | not provided |