Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000520061 | SCV000616953 | likely pathogenic | not provided | 2020-06-02 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016); Missense variants in this gene are often considered pathogenic (Stenson et al., 2014); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This substitution is predicted to be within the transmembrane segment S1 of the third homologous domain; Has not been previously published as pathogenic or benign to our knowledge |
Invitae | RCV000706305 | SCV000835347 | uncertain significance | Early infantile epileptic encephalopathy with suppression bursts | 2020-01-24 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant identified in the SCN1A gene is located in the transmembrane spanning D3-S1 region of the resulting protein (PMID: 25348405, 18804930), but it is unclear how this variant impacts the function of this protein. This variant has not been reported in the literature in individuals with SCN1A-related disease. ClinVar contains an entry for this variant (Variation ID: 449140). This variant is not present in population databases (ExAC no frequency). This sequence change replaces phenylalanine with serine at codon 1237 of the SCN1A protein (p.Phe1237Ser). The phenylalanine residue is highly conserved and there is a large physicochemical difference between phenylalanine and serine. |