ClinVar Miner

Submissions for variant NM_005188.4(CBL):c.1111T>A (p.Tyr371Asn)

dbSNP: rs267606706
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000506397 SCV000602914 likely pathogenic not specified 2017-02-02 criteria provided, single submitter clinical testing
Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn RCV000856726 SCV000999271 pathogenic Noonan syndrome 1 criteria provided, single submitter clinical testing
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center RCV001814073 SCV002061465 likely pathogenic CBL-related disorder 2021-08-02 criteria provided, single submitter clinical testing PS2, PM2, PM5
Laboratory of Molecular Genetics (Pr. Bezieau's lab), CHU de Nantes RCV002277316 SCV002564535 pathogenic Neurodevelopmental disorder 2022-06-08 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003539801 SCV004294979 likely pathogenic RASopathy 2023-04-24 criteria provided, single submitter clinical testing In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Tyr371 amino acid residue in CBL. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 20543203, 20694012, 25283271, 25952305, 28414188). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 expected to disrupt CBL protein function. ClinVar contains an entry for this variant (Variation ID: 180827). This missense change has been observed in individual(s) with cerebral arteriopathy and/or juvenile myelomonocytic leukemia (PMID: 20694012, 28343148). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 371 of the CBL protein (p.Tyr371Asn).

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