Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000463674 | SCV000551884 | pathogenic | Seizures, benign familial infantile, 3; Developmental and epileptic encephalopathy, 11 | 2022-08-16 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1659 of the SCN2A protein (p.Ala1659Val). This missense change has been observed in individual(s) with clinical features of early infantile epileptic encephalopathy (Invitae). In at least one individual the variant was observed to be de novo. For these reasons, this variant has been classified as Pathogenic. 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: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 410984). |
| Institute of Medical Genetics and Applied Genomics, |
RCV001268119 | SCV001446779 | likely pathogenic | not provided | 2020-10-23 | criteria provided, single submitter | clinical testing | |
| Beijing Key Laboratry for Genetics of Birth Defects, |
RCV001530194 | SCV001739486 | likely pathogenic | Seizures, benign familial infantile, 3 | 2020-02-28 | criteria provided, single submitter | clinical testing | |
| 3billion | RCV003313957 | SCV004013800 | likely pathogenic | Developmental and epileptic encephalopathy, 11 | criteria provided, single submitter | clinical testing | The variant is not observed in the gnomAD v2.1.1 dataset. The variant is located in a mutational hot spot and/or well-established functional domain in which established pathogenic variants have been reported. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.91; 3Cnet: 0.99). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000410984). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline. | |
| Génétique des Maladies du Développement, |
RCV001003339 | SCV001156233 | pathogenic | Seizure | 2020-02-03 | no assertion criteria provided | clinical testing | 20% mosacism |