ClinVar Miner

Submissions for variant NM_005188.4(CBL):c.2584G>A (p.Glu862Lys)

gnomAD frequency: 0.00001  dbSNP: rs397507498
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000033374 SCV000057279 uncertain significance not provided 2012-07-19 criteria provided, single submitter clinical testing This variant is denoted p.Glu863Lys at the protein level, c.2584G>A at the cDNA level, and results in the change of a Glutamic acid for a Lysine (GAG>AAG) in exon 16 of the CBL gene (NM_00005188.2). The E862K missense change is a non-conservative amino acid substitution with a positively-charged residue (Lys) replacing a negatively-charged residue (Glu). The position at which this substitution occurs is conserved in the protein but not in related proteins. The E862K missense change occurs with the ubiquitin-associated domain of the protein; however, no missense mutations have been reported in the CBL gene beyond codon Arginine 420 (Martinelli et al., 2010).With the current information, we interpret E862K as a variant of unknown significance. The variant is found in NOONAN panel(s).
Labcorp Genetics (formerly Invitae), Labcorp RCV001223148 SCV001395283 uncertain significance RASopathy 2024-12-20 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 862 of the CBL protein (p.Glu862Lys). This variant is present in population databases (rs397507498, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with CBL-related conditions. ClinVar contains an entry for this variant (Variation ID: 40426). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt CBL protein function with a negative predictive value of 95%. 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.
Fulgent Genetics, Fulgent Genetics RCV002504855 SCV002816337 uncertain significance Juvenile myelomonocytic leukemia; CBL-related disorder 2021-10-06 criteria provided, single submitter clinical testing

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