ClinVar Miner

Submissions for variant NM_005188.4(CBL):c.1463C>T (p.Ala488Val)

gnomAD frequency: 0.00002  dbSNP: rs377502790
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000106326 SCV000367762 uncertain significance CBL-related disorder 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Fulgent Genetics, Fulgent Genetics RCV000763710 SCV000894590 uncertain significance Juvenile myelomonocytic leukemia; CBL-related disorder 2018-10-31 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV001813377 SCV002060746 uncertain significance Noonan syndrome and Noonan-related syndrome 2016-12-12 criteria provided, single submitter clinical testing
Invitae RCV001854518 SCV002109450 uncertain significance RASopathy 2023-09-26 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 488 of the CBL protein (p.Ala488Val). This variant is present in population databases (rs377502790, 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: 120247). 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. 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.
Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP) RCV000106326 SCV000143824 not provided CBL-related disorder no assertion provided not provided

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