Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000189011 | SCV000242642 | uncertain significance | not provided | 2023-05-02 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (gnomAD); The majority of missense variants in this gene are considered pathogenic (HGMD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This substitution is predicted to be within the N/C-terminal cytoplasmic domain |
| Invitae | RCV000697361 | SCV000825965 | likely pathogenic | Early infantile epileptic encephalopathy with suppression bursts | 2023-12-27 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 1874 of the SCN1A protein (p.Arg1874Trp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of autosomal dominant SCN1A-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 206873). 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.Arg1874 amino acid residue in SCN1A. Other variant(s) that disrupt this residue have been observed in individuals with SCN1A-related conditions (PMID: 31765958; Invitae), which suggests that this may be a clinically significant amino acid residue. 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. |
| Génétique des Maladies du Développement, |
RCV002227087 | SCV002506558 | likely pathogenic | Generalized epilepsy with febrile seizures plus, type 2 | no assertion criteria provided | clinical testing |