Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000189240 | SCV000242872 | uncertain significance | not provided | 2022-04-11 | 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 has a deleterious effect on protein structure/function; This substitution is predicted to be within the C-terminal cytoplasmic domain; Has not been previously published as pathogenic or benign to our knowledge |
Invitae | RCV001070208 | SCV001235425 | uncertain significance | Seizures, benign familial infantile, 3; Developmental and epileptic encephalopathy, 11 | 2023-06-30 | criteria provided, single submitter | clinical testing | 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 SCN2A protein function. ClinVar contains an entry for this variant (Variation ID: 207085). This variant has not been reported in the literature in individuals affected with SCN2A-related conditions. This variant is present in population databases (rs547095921, gnomAD 0.003%). This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 1838 of the SCN2A protein (p.Gln1838His). 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. |