Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001065358 | SCV001230314 | uncertain significance | Developmental and epileptic encephalopathy, 9 | 2020-05-04 | 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. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PCDH19 are known to be pathogenic (PMID: 21053371). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with PCDH19-related conditions, but it has been observed in several unaffected females (Invitae). ClinVar contains an entry for this variant (variation ID: 859285). This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in intron 2 of the PCDH19 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. |
| Athena Diagnostics Inc | RCV001289114 | SCV001476721 | likely pathogenic | not provided | 2019-08-29 | criteria provided, single submitter | clinical testing | The variant disrupts a canonical splice site, and is therefore predicted to result in the loss of a functional protein. Not found in the total gnomAD dataset, and the data is high quality. |