Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000686945 | SCV000814487 | uncertain significance | Seizures, benign familial infantile, 3; Developmental and epileptic encephalopathy, 11 | 2020-02-17 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with SCN2A-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with methionine at codon 1059 of the SCN2A protein (p.Ile1059Met). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and methionine. Algorithms developed to predict the effect of missense changes on protein structure and function 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. |