Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001377142 | SCV001574383 | likely pathogenic | Intellectual disability, autosomal dominant 20 | 2023-11-27 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 6 of the MEF2C gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MEF2C are known to be pathogenic (PMID: 20513142). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with seizures, infantile spasms, and motor developmental delay (Invitae). ClinVar contains an entry for this variant (Variation ID: 1066205). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Gene |
RCV003442877 | SCV004169701 | pathogenic | not provided | 2023-04-03 | criteria provided, single submitter | clinical testing | Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge |