Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000806199 | SCV000946185 | uncertain significance | Early infantile epileptic encephalopathy with suppression bursts | 2023-11-19 | 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 1912 of the SCN1A protein (p.Arg1912Gln). This variant is present in population databases (rs373896263, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with SCN1A-related conditions. ClinVar contains an entry for this variant (Variation ID: 650943). 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 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. |
Ambry Genetics | RCV001266647 | SCV001444823 | uncertain significance | Inborn genetic diseases | 2019-09-08 | criteria provided, single submitter | clinical testing | |
Centre for Inherited Metabolic Diseases, |
RCV001375624 | SCV001572546 | uncertain significance | Generalized epilepsy with febrile seizures plus, type 2 | 2021-04-25 | criteria provided, single submitter | clinical testing | Considered to be causative of the patients phenotype. The father is also a carrier and he had febrile seizures. |
Gene |
RCV001585733 | SCV001819356 | uncertain significance | not provided | 2023-10-16 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign in association with epilepsy to our knowledge; Not observed at a significant frequency in large population cohorts (gnomAD); This substitution is predicted to be within the C-terminal cytoplasmic domain.; 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: 33726816) |