Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000189266 | SCV000242898 | likely pathogenic | not provided | 2019-09-30 | criteria provided, single submitter | clinical testing | The majority of missense variants in this gene are considered pathogenic (Stenson et al., 2014); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 29655203) |
Invitae | RCV002517014 | SCV003472603 | uncertain significance | Early infantile epileptic encephalopathy with suppression bursts | 2023-11-27 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 845 of the SCN8A protein (p.Ser845Phe). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of SCN8A-related conditions (PMID: 29655203). ClinVar contains an entry for this variant (Variation ID: 207109). 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 SCN8A protein function with a positive predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Duke University Health System Sequencing Clinic, |
RCV003223395 | SCV003919061 | likely pathogenic | Developmental and epileptic encephalopathy, 13 | 2023-04-20 | criteria provided, single submitter | research |