Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000818571 | SCV000959191 | pathogenic | Seizures, benign familial infantile, 3; Developmental and epileptic encephalopathy, 11 | 2020-01-17 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). For these reasons, this variant has been classified as Pathogenic. 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. This variant has been observed in individual(s) with early-onset epileptic encephalopathy with Rett-like features (PMID: 28709814). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 661206). This sequence change replaces valine with methionine at codon 424 of the SCN2A protein (p.Val424Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. |
| 3billion | RCV003152737 | SCV003841878 | pathogenic | Developmental and epileptic encephalopathy, 11 | 2023-02-23 | criteria provided, single submitter | clinical testing | The variant is not observed in the gnomAD v2.1.1 dataset. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.80; 3Cnet: 1.00). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with SCN2A related disorder (ClinVar ID: VCV000661206 / PMID: 28709814). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. |