Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV005068427 | SCV005706376 | uncertain significance | RASopathy | 2024-04-16 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 166 of the CBL protein (p.Lys166Arg). This variant is present in population databases (rs750257998, gnomAD 0.01%). 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) 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 CBL 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. |
| Ambry Genetics | RCV005311170 | SCV005980868 | uncertain significance | Cardiovascular phenotype | 2025-02-10 | criteria provided, single submitter | clinical testing | The p.K166R variant (also known as c.497A>G), located in coding exon 3 of the CBL gene, results from an A to G substitution at nucleotide position 497. The lysine at codon 166 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |