Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001045388 | SCV001209237 | likely pathogenic | Early infantile epileptic encephalopathy with suppression bursts | 2024-06-05 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 139 of the SCN1A protein (p.Leu139Phe). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of SCN1A-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 842887). 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. |
| Gene |
RCV003227900 | SCV003924642 | likely pathogenic | not provided | 2023-05-11 | criteria provided, single submitter | clinical testing | Missense variants in this gene are often considered pathogenic (HGMD); This substitution is predicted to be within the transmembrane segment S1 of the first homologous domain; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge |