Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001232779 | SCV001405347 | uncertain significance | Seizures, benign familial infantile, 3; Developmental and epileptic encephalopathy, 11 | 2024-11-18 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 916 of the SCN2A protein (p.Asn916Ser). This variant is present in population databases (rs763684457, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with SCN2A-related conditions. ClinVar contains an entry for this variant (Variation ID: 959426). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt SCN2A protein function with a negative 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. |
| Gene |
RCV001751456 | SCV002005048 | uncertain significance | not provided | 2019-12-04 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); 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 that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This substitution is predicted to be within the extracellular loop between the S5 and S6 transmembrane segments of the second homologous domain |
| Ambry Genetics | RCV004033181 | SCV004944212 | uncertain significance | Inborn genetic diseases | 2024-03-07 | criteria provided, single submitter | clinical testing | The c.2747A>G (p.N916S) alteration is located in exon 16 (coding exon 15) of the SCN2A gene. This alteration results from a A to G substitution at nucleotide position 2747, causing the asparagine (N) at amino acid position 916 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |