Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Hudson |
RCV000144154 | SCV000297794 | pathogenic | Developmental and epileptic encephalopathy, 13 | 2016-07-14 | criteria provided, single submitter | research | |
Gene |
RCV000522954 | SCV000616869 | pathogenic | not provided | 2021-10-22 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate a damaging effect resulting in channel hyperactivity (Wagnon et al., 2016); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Missense variants in this gene are often considered pathogenic (HGMD); This variant is associated with the following publications: (PMID: 31692161, 25785782, 24194747, 26029160, 23020937, 24888894, 25568300, 25046240, 28554332, 29588952, 30171078, 28191890, 29655203, 32090326, 31175295, 33004838, 33442870, 26900580) |
Invitae | RCV000636307 | SCV000757746 | pathogenic | Early infantile epileptic encephalopathy with suppression bursts | 2024-01-24 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1617 of the SCN8A protein (p.Arg1617Gln). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with epileptic encephalopathies (PMID: 23020937, 24888894, 25046240, 25568300, 25785782, 26029160, 29588952). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 156106). 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%. Experimental studies have shown that this missense change affects SCN8A function (PMID: 26900580). For these reasons, this variant has been classified as Pathogenic. |
Ambry Genetics | RCV001266283 | SCV001444456 | pathogenic | Inborn genetic diseases | 2019-07-18 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000144154 | SCV000189234 | pathogenic | Developmental and epileptic encephalopathy, 13 | 2014-07-01 | no assertion criteria provided | literature only | |
Gene |
RCV000144154 | SCV000298208 | not provided | Developmental and epileptic encephalopathy, 13 | no assertion provided | literature only | ||
Clinical Molecular Genetics Laboratory, |
RCV000678845 | SCV000805036 | uncertain significance | developmental delay with seizures | 2017-08-25 | no assertion criteria provided | clinical testing |