Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000766785 | SCV000590382 | uncertain significance | not provided | 2022-02-02 | criteria provided, single submitter | clinical testing | Not observed at a 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; Has not been previously published as pathogenic or benign to our knowledge; This substitution is predicted to be within the C-terminal cytoplasmic domain |
Genetic Services Laboratory, |
RCV000497883 | SCV000596944 | uncertain significance | not specified | 2015-08-10 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001066109 | SCV001231106 | uncertain significance | Early infantile epileptic encephalopathy with suppression bursts | 2022-06-20 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 432633). This variant has not been reported in the literature in individuals affected with SCN1A-related conditions. This variant is present in population databases (rs148703212, gnomAD 0.003%). This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 1878 of the SCN1A protein (p.Glu1878Gln). |
Prevention |
RCV003409688 | SCV004112203 | uncertain significance | SCN1A-related condition | 2023-06-27 | criteria provided, single submitter | clinical testing | The SCN1A c.5632G>C variant is predicted to result in the amino acid substitution p.Glu1878Gln. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0035% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-166848153-C-G). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |