Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| SIB Swiss Institute of Bioinformatics | RCV000656390 | SCV000883212 | likely pathogenic | Developmental and epileptic encephalopathy, 65 | 2018-10-15 | criteria provided, single submitter | curation | This variant is interpreted as Likely Pathogenic, for Epileptic encephalopathy, early infantile, 65, autosomal dominant. The following ACMG Tag(s) were applied: PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PM1 => Located in a mutational hot spot and/or critical and well-established functional domain (e.g., active site of an enzyme) without benign variation (https://www.ncbi.nlm.nih.gov/pubmed/29534297). PS2 => De novo (paternity and maternity confirmed) (https://www.ncbi.nlm.nih.gov/pubmed/29534297). |
| Invitae | RCV001384044 | SCV001583414 | pathogenic | not provided | 2018-04-17 | 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. The p.Arg87 amino acid residue in CYFIP2 has been determined to be clinically significant (PMID: 29534297, 29667327). This suggests that variants that disrupt this residue are likely to be causative of disease. 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: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has been reported to be de novo in an individual affected with Ohtahara syndrome (PMID: 29534297). This sequence change replaces arginine with proline at codon 87 of the CYFIP2 protein (p.Arg87Pro). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and proline. |
| OMIM | RCV000656390 | SCV000778396 | pathogenic | Developmental and epileptic encephalopathy, 65 | 2020-11-17 | no assertion criteria provided | literature only |