Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002297900 | SCV002591928 | uncertain significance | not provided | 2022-09-22 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 105 of the NOTCH3 protein (p.Ser105Pro). This variant has not been reported in the literature in individuals affected with NOTCH3-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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on NOTCH3 protein function. 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. |
Centre for Clinical Genetics and Genomic Diagnostics, |
RCV002297900 | SCV005328469 | uncertain significance | not provided | 2024-08-05 | criteria provided, single submitter | clinical testing |