Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000700639 | SCV000829402 | uncertain significance | Febrile seizures, familial, 11 | 2018-04-03 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine with valine at codon 43 of the CPA6 protein (p.Ile43Val). The isoleucine residue is weakly conserved and there is a small physicochemical difference between isoleucine and valine. This variant is present in population databases (rs766547893, ExAC 0.006%). This variant has not been reported in the literature in individuals with CPA6-related disease. 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. 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. 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. |
Institute of Human Genetics, |
RCV000700639 | SCV002026372 | uncertain significance | Febrile seizures, familial, 11 | 2021-11-05 | criteria provided, single submitter | clinical testing | _x000D_This variant was identified as compound heterozygous with NM_020361.5:c.127A>G. Criteria applied: PM3, PM2_SUP |
New York Genome Center | RCV002227489 | SCV002506953 | uncertain significance | Familial temporal lobe epilepsy 5; Febrile seizures, familial, 11 | 2021-05-14 | criteria provided, single submitter | clinical testing |