Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001227247 | SCV001399598 | uncertain significance | Early infantile epileptic encephalopathy with suppression bursts | 2020-03-12 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed in individual(s) with a diagnosis or clinical features of Dravet syndrome (PMID: 27197941, Invitae). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (ExAC no frequency). This sequence change replaces asparagine with threonine at codon 1845 of the SCN1A protein (p.Asn1845Thr). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and threonine. |
| Mendelics | RCV002249814 | SCV002519307 | uncertain significance | not specified | 2022-05-04 | criteria provided, single submitter | clinical testing |