Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003768495 | SCV000938155 | uncertain significance | Absence seizure; Myoclonic epilepsy, juvenile, susceptibility to, 1 | 2018-09-20 | 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with EFHC1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces methionine with isoleucine at codon 516 of the EFHC1 protein (p.Met516Ile). The methionine residue is moderately conserved and there is a small physicochemical difference between methionine and isoleucine. |