Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Athena Diagnostics Inc | RCV000992226 | SCV001144317 | likely pathogenic | not provided | 2019-06-05 | criteria provided, single submitter | clinical testing | Not found in the total gnomAD dataset, and the data is high quality (0/279694 chr). Predicted to have a damaging effect on the protein. Located in potentially critical domain of the protein. Moderate co-segregation with disease in affected and unaffected individuals, but from a single family. |
| Invitae | RCV001046813 | SCV001210730 | uncertain significance | Early infantile epileptic encephalopathy with suppression bursts | 2020-06-15 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with proline at codon 581 of the KCNQ2 protein (p.Arg581Pro). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and proline. This variant is not present in population databases (ExAC no frequency). 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. This variant disrupts the p.Arg581 amino acid residue in KCNQ2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 25262651, 29186148, 25262651). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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"). This variant has not been reported in the literature in individuals with KCNQ2-related conditions. |