Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000470807 | SCV000548106 | pathogenic | Angelman syndrome | 2016-06-17 | criteria provided, single submitter | clinical testing | This sequence change deletes 17 nucleotides in exon 10 of the UBE3A mRNA (c.2475_2491delACTTCCGGAATACTCAA), causing a frameshift at codon 826. This creates a premature translational stop signal in the last exon of the UBE3A mRNA (p.Leu826Glnfs*5). While this is not anticipated to result in nonsense mediated decay, it is expected to result in a truncated UBE3A protein. While this particular variant has not been reported in the literature, maternally-inherited truncating variants in UBE3A are known to be pathogenic (PMID: 25212744). In addition, several frameshift variants that occur downstream of this variant have been reported in affected individuals (PMID: 25212744). For these reasons, this variant has been classified as Pathogenic. |