Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000228705 | SCV000289933 | likely pathogenic | Early infantile epileptic encephalopathy with suppression bursts | 2017-04-11 | criteria provided, single submitter | clinical testing | Family studies have indicated that this variant was not present in the parents of an individual with clinical features consistent with an SCN8A-related disease, which suggests that it was de novo in that affected individual. This sequence change replaces glutamine with proline at codon 417 of the SCN8A protein (p.Gln417Pro). The glutamine residue is highly conserved and there is a moderate physicochemical difference between glutamine and proline. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a SCN8A-related 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: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a novel missense change that has been observed to occur de novo in an affected individual. This evidence indicates that the variant is pathogenic, but additional data is needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Ambry Genetics | RCV000622388 | SCV000742422 | uncertain significance | Inborn genetic diseases | 2017-04-13 | criteria provided, single submitter | clinical testing |