Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000188847 | SCV000242477 | uncertain significance | not provided | 2021-01-11 | criteria provided, single submitter | clinical testing | This substitution is predicted to be within the transmembrane segment S5 of the first homologous 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 (Stenson et al., 2014); This variant is associated with the following publications: (PMID: 29655203) |
Eurofins Ntd Llc |
RCV000188847 | SCV000332464 | uncertain significance | not provided | 2015-07-16 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001052796 | SCV001217022 | uncertain significance | Early infantile epileptic encephalopathy with suppression bursts | 2024-09-08 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 264 of the SCN1A protein (p.Ile264Thr). This variant is present in population databases (rs745664511, gnomAD 0.01%). This missense change has been observed in individual(s) with SCN1A-related disease (PMID: 29655203). This missense change has been observed in at least one individual who was not affected with SCN1A-related conditions (internal data). ClinVar contains an entry for this variant (Variation ID: 206748). 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 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. |