Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Athena Diagnostics | RCV001288892 | SCV001476291 | pathogenic | not provided | 2020-08-20 | criteria provided, single submitter | clinical testing | The variant disrupts a cysteine residue in an EGF-like repeat domain, which is important for the structure of this protein. Therefore it is expected to severely affect the function of the protein. Found in at least one patient with expected phenotype for this gene, and not found in general population data. |
| Labcorp Genetics |
RCV001288892 | SCV002278171 | uncertain significance | not provided | 2020-12-20 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine with serine at codon 1022 of the NOTCH3 protein (p.Cys1022Ser). The cysteine residue is highly conserved and there is a moderate physicochemical difference between cysteine and serine. This variant is not present in population databases (ExAC no frequency). 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 expected to disrupt NOTCH3 protein function. This variant has not been reported in the literature in individuals with NOTCH3-related conditions. |