Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000439062 | SCV000536594 | uncertain significance | not provided | 2023-01-16 | 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); Has not been previously published as pathogenic or benign to our knowledge; This substitution is predicted to be within the intracellular loop between the second and third repeat; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function |
Invitae | RCV001851107 | SCV002279437 | uncertain significance | Early infantile epileptic encephalopathy with suppression bursts | 2021-12-15 | 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. ClinVar contains an entry for this variant (Variation ID: 393218). This variant has not been reported in the literature in individuals affected with SCN1A-related conditions. This variant is present in population databases (rs376649518, gnomAD 0.002%). This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 1041 of the SCN1A protein (p.Lys1041Glu). |