Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000823778 | SCV000964648 | pathogenic | Seizures, benign familial infantile, 3; Developmental and epileptic encephalopathy, 11 | 2020-01-17 | criteria provided, single submitter | clinical testing | This variant has been observed in individual(s) with early infantile epileptic encephalopathy (PMID: 28379373, 27652284). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 665483). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamine with glutamic acid at codon 1811 of the SCN2A protein (p.Gln1811Glu). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and glutamic acid. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SCN2A protein function. For these reasons, this variant has been classified as Pathogenic. |