Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000144315 | SCV000964232 | likely pathogenic | Angelman syndrome | 2022-09-05 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available"). ClinVar contains an entry for this variant (Variation ID: 155992). This variant is also known as c.2540C>T. This missense change has been observed in individuals with clinical features of Angelman syndrome and Angelman syndome (PMID: 25212744, 29188609). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 827 of the UBE3A protein (p.Pro827Leu). |
| Ambry Genetics | RCV002514772 | SCV003572172 | likely pathogenic | Inborn genetic diseases | 2021-09-29 | criteria provided, single submitter | clinical testing | The c.2480C>T (p.P827L) alteration is located in exon 10 (coding exon 10) of the UBE3A gene. This alteration results from a C to T substitution at nucleotide position 2480, causing the proline (P) at amino acid position 827 to be replaced by a leucine (L). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This alteration has been reported in multiple unrelated patients with features consistent with Angelman syndrome, including at least one presumed de novo occurrence (Sadikovic, 2014; Xu, 2017; internal data; personal communication). This amino acid position is highly conserved in available vertebrate species. The in silico prediction for this alteration is inconclusive. Based on the available evidence, this alteration is classified as likely pathogenic. |
| Laboratory of Molecular Genetics |
RCV003389042 | SCV004101149 | pathogenic | Neurodevelopmental disorder | 2023-07-26 | criteria provided, single submitter | clinical testing | |
| Molecular Genetics Lab, |
RCV000144315 | SCV004697584 | pathogenic | Angelman syndrome | criteria provided, single submitter | clinical testing | ||
| Baylor Genetics | RCV000144315 | SCV000172066 | pathogenic | Angelman syndrome | 2014-02-14 | no assertion criteria provided | clinical testing |