Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Center for Pediatric Genomic Medicine, |
RCV000514203 | SCV000611021 | pathogenic | not provided | 2017-09-06 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001044278 | SCV001208068 | pathogenic | Angelman syndrome | 2020-01-25 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in UBE3A are known to be pathogenic (PMID: 25212744). This variant has been observed in several individuals with clinical features of Angelman syndrome (PMID: 9585605, 25212744, Invitae). ClinVar contains an entry for this variant (Variation ID: 446052). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Arg482*) in the UBE3A gene. It is expected to result in an absent or disrupted protein product. |
3billion | RCV001044278 | SCV002059048 | pathogenic | Angelman syndrome | 2022-01-03 | criteria provided, single submitter | clinical testing | Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant (PVS1_VS). It is not observed in the gnomAD v2.1.1 dataset (PM2_M). The variant has been reported at least twice as pathogenic/likely pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000446052, PMID:9585605). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. |