ClinVar Miner

Submissions for variant NM_005188.3(CBL):c.1112A>C (p.Tyr371Ser) (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 Genetic Testing Laboratories,Mayo Clinic RCV000660642 SCV000782765 pathogenic Juvenile myelomonocytic leukemia; Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia 2018-01-26 criteria provided, single submitter clinical testing
Baylor Genetics RCV000660642 SCV000992701 likely pathogenic Juvenile myelomonocytic leukemia; Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia 2018-10-12 criteria provided, single submitter clinical testing
Invitae RCV001042520 SCV001206203 uncertain significance Rasopathy 2019-03-17 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with serine at codon 371 of the CBL protein (p.Tyr371Ser). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in the germline of individuals with CBL-related conditions. ClinVar contains an entry for this variant (Variation ID: 548022). This variant has been reported to affect CBL protein function (PMID:27609087, 19620960). 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. 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.

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