Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV005537810 | SCV006209042 | uncertain significance | Cardiovascular phenotype | 2025-05-27 | criteria provided, single submitter | clinical testing | The p.N795D variant (also known as c.2383A>G), located in coding exon 15 of the CBL gene, results from an A to G substitution at nucleotide position 2383. The asparagine at codon 795 is replaced by aspartic acid, an amino acid with highly similar 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. |
| Labcorp Genetics |
RCV005167589 | SCV005794243 | uncertain significance | RASopathy | 2024-05-08 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 795 of the CBL protein (p.Asn795Asp). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CBL-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 CBL protein function with a negative predictive value of 95%. 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. |