Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001951695 | SCV002247105 | uncertain significance | Hajdu-Cheney syndrome | 2021-06-28 | criteria provided, single submitter | clinical testing | 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. 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 not expected to disrupt NOTCH2 protein function. This variant has not been reported in the literature in individuals with NOTCH2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with leucine at codon 900 of the NOTCH2 protein (p.Pro900Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. |
Fulgent Genetics, |
RCV002507708 | SCV002816647 | uncertain significance | Alagille syndrome due to a NOTCH2 point mutation; Hajdu-Cheney syndrome | 2021-11-16 | criteria provided, single submitter | clinical testing |