ClinVar Miner

Submissions for variant NM_005188.4(CBL):c.1112A>C (p.Tyr371Ser)

dbSNP: rs387906666
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mayo Clinic Laboratories, Mayo Clinic RCV000660642 SCV000782765 pathogenic Juvenile myelomonocytic leukemia; CBL-related disorder 2018-01-26 criteria provided, single submitter clinical testing
Baylor Genetics RCV000660642 SCV000992701 likely pathogenic Juvenile myelomonocytic leukemia; CBL-related disorder 2018-10-12 criteria provided, single submitter clinical testing
Invitae RCV001042520 SCV001206203 likely pathogenic RASopathy 2022-11-29 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. Experimental studies have shown that this missense change affects CBL function (PMID: 19620960, 27609087). 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: 548022). This missense change has been observed in individual(s) with clinical features of Noonan syndrome (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with serine, which is neutral and polar, at codon 371 of the CBL protein (p.Tyr371Ser).

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