Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000636336 | SCV000757775 | likely pathogenic | Early infantile epileptic encephalopathy with suppression bursts | 2020-03-21 | criteria provided, single submitter | clinical testing | 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. This variant identified in the SCN1A gene is located in the cytoplasmic D1-S2/S3 region of the resulting protein (PMID: 25348405, 18804930). Experimental studies have shown that this missense change decreased entry into and increased rate of recovery from slow inactivated state, and disrupted normal sodium channel function (PMID: 12576172, 16075041, 20550552). This variant has been reported in the literature in individuals with generalized epilepsy with febrile seizures plus (GEFS) and Dravet syndrome (PMID: 11254444, 12576172, 22780858). It has been shown to co-segregate with GEFS in an affected families, but the segregation was considered incomplete because two unaffected individuals carry this variant (PMID: 11254444). ClinVar contains an entry for this variant (Variation ID: 12884). This variant is not present in population databases (ExAC no frequency). This sequence change replaces aspartic acid with valine at codon 188 of the SCN1A protein (p.Asp188Val). The aspartic acid residue is highly conserved and there is a large physicochemical difference between aspartic acid and valine. |
| OMIM | RCV000013744 | SCV000033991 | pathogenic | Generalized epilepsy with febrile seizures plus, type 2 | 2001-04-01 | no assertion criteria provided | literature only | |
| Uni |
RCV000059448 | SCV000090973 | not provided | Generalized epilepsy with febrile seizures plus, type 1 | no assertion provided | not provided |