Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Revvity Omics, |
RCV003488152 | SCV004235617 | uncertain significance | not provided | 2023-02-10 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV003523210 | SCV004335609 | uncertain significance | Hajdu-Cheney syndrome | 2024-04-14 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1488 of the NOTCH2 protein (p.Glu1488Lys). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with NOTCH2-related conditions. 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 with a negative predictive value of 80%. 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. |
| Gene |
RCV003488152 | SCV005081553 | uncertain significance | not provided | 2023-08-17 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Fulgent Genetics, |
RCV005030063 | SCV005648026 | uncertain significance | Alagille syndrome due to a NOTCH2 point mutation; Hajdu-Cheney syndrome | 2024-03-28 | criteria provided, single submitter | clinical testing |