Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002912507 | SCV003246698 | uncertain significance | RASopathy | 2021-12-02 | 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 CBL protein function. This variant has not been reported in the literature in individuals affected with CBL-related conditions. This variant is present in population databases (rs760490210, gnomAD 0.008%). This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 606 of the CBL protein (p.Ser606Arg). |
| Ambry Genetics | RCV004990901 | SCV005545845 | uncertain significance | Cardiovascular phenotype | 2024-12-02 | criteria provided, single submitter | clinical testing | The p.S606R variant (also known as c.1818T>A), located in coding exon 11 of the CBL gene, results from a T to A substitution at nucleotide position 1818. The serine at codon 606 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |