Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002033152 | SCV002116117 | uncertain significance | RASopathy | 2023-05-16 | 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. ClinVar contains an entry for this variant (Variation ID: 1347603). This variant has not been reported in the literature in individuals affected with CBL-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 834 of the CBL protein (p.Glu834Asp). |
Fulgent Genetics, |
RCV002503352 | SCV002778310 | uncertain significance | Juvenile myelomonocytic leukemia; CBL-related disorder | 2021-08-11 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV004038771 | SCV005022972 | uncertain significance | Cardiovascular phenotype | 2024-01-29 | criteria provided, single submitter | clinical testing | The p.E834D variant (also known as c.2502A>T), located in coding exon 16 of the CBL gene, results from an A to T substitution at nucleotide position 2502. The glutamic acid at codon 834 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this alteration remains unclear. |