Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000689911 | SCV000817581 | likely pathogenic | Early infantile epileptic encephalopathy with suppression bursts | 2024-01-03 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1595 of the SCN1A protein (p.Leu1595Ile). This variant is present in population databases (rs756238700, gnomAD 0.002%). This missense change has been observed in individuals with clinical features of autosomal dominant SCN1A-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 569312). 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%. 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. |
Ce |
RCV002263933 | SCV002544106 | uncertain significance | not provided | 2022-06-01 | criteria provided, single submitter | clinical testing | SCN1A: PP2 |
Gene |
RCV002263933 | SCV003195062 | uncertain significance | not provided | 2023-01-11 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); Missense variants in this gene are often considered pathogenic (HGMD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This substitution is predicted to be within the intracellular loop between the S2 and S3 transmembrane segments of the fourth homologous domain |