ClinVar Miner

Submissions for variant NM_005188.4(CBL):c.286C>T (p.Arg96Cys)

gnomAD frequency: 0.00002  dbSNP: rs147438359
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001317530 SCV001508196 uncertain significance RASopathy 2024-06-05 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 96 of the CBL protein (p.Arg96Cys). This variant is present in population databases (rs147438359, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with CBL-related conditions. ClinVar contains an entry for this variant (Variation ID: 1018257). 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.
AiLife Diagnostics, AiLife Diagnostics RCV002224059 SCV002502977 uncertain significance not provided 2021-11-15 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002476480 SCV002794534 uncertain significance Juvenile myelomonocytic leukemia; CBL-related disorder 2021-10-07 criteria provided, single submitter clinical testing
Ambry Genetics RCV003166829 SCV003855258 uncertain significance Cardiovascular phenotype 2024-11-24 criteria provided, single submitter clinical testing The p.R96C variant (also known as c.286C>T), located in coding exon 2 of the CBL gene, results from a C to T substitution at nucleotide position 286. The arginine at codon 96 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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