Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Mayo Clinic Laboratories, |
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 | |
Labcorp Genetics |
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). |
Gene |
RCV004721531 | SCV005326734 | pathogenic | not provided | 2024-02-27 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate the variant results in abnormal protein function (PMID: 19620960); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 27609087, 33627783, 20501843, 31216405, 22131879, 33144682, 19620960, 20619386, 22315494) |