Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001239285 | SCV001412144 | uncertain significance | Seizures, benign familial infantile, 3; Developmental and epileptic encephalopathy, 11 | 2019-11-01 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid with glutamic acid at codon 1487 of the SCN2A protein (p.Asp1487Glu). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has been observed as de novo in individual(s) with autism spectrum disorder (PMID: 30564305). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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 |
RCV003236882 | SCV003935699 | pathogenic | not provided | 2023-06-23 | 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); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This substitution is predicted to be within the cytoplasmic loop between the third and fourth homologous domains; This variant is associated with the following publications: (PMID: 30564305, 33731876, 32603808) |