ClinVar Miner

Submissions for variant NM_005188.4(CBL):c.1150T>C (p.Cys384Arg)

dbSNP: rs387906664
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001561040 SCV001783561 pathogenic not provided 2024-08-19 criteria provided, single submitter clinical testing Published functional studies demonstrated p.C384R damages the capacity of the polyubiquitylation of pEGFR (PMID: 20694012); 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: 19571318, 24803665, 20619386, 20694012, 23696637, 20644105, 22315494, 22733026)
Labcorp Genetics (formerly Invitae), Labcorp RCV001857355 SCV002172326 uncertain significance RASopathy 2023-06-03 criteria provided, single submitter clinical testing 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. Experimental studies have shown that this missense change affects CBL function (PMID: 20694012, 23696637). 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: 29822). This missense change has been observed in individual(s) with clinical features of Noonan-like syndrome with or without juvenile myelomonocytic leukemia (PMID: 19571318, 20694012). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 384 of the CBL protein (p.Cys384Arg).
OMIM RCV000022698 SCV000043987 pathogenic Noonan syndrome-like disorder with juvenile myelomonocytic leukemia 2010-09-01 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000420743 SCV000505200 likely pathogenic Hematologic neoplasm 2014-12-26 no assertion criteria provided literature only

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