Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Diagnostic Laboratory, |
RCV001260797 | SCV001437890 | likely benign | Intellectual disability | 2020-09-10 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV003509663 | SCV004292866 | uncertain significance | Angelman syndrome | 2023-11-03 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 732 of the UBE3A protein (p.Ile732Thr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with UBE3A-related conditions. ClinVar contains an entry for this variant (Variation ID: 981393). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt UBE3A protein function with a positive predictive value of 95%. 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. |