ClinVar Miner

Submissions for variant NM_005188.4(CBL):c.2692A>G (p.Ile898Val)

gnomAD frequency: 0.00001  dbSNP: rs397507499
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000033376 SCV000057281 uncertain significance not provided 2024-05-16 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV000533281 SCV000659118 uncertain significance RASopathy 2023-11-19 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 898 of the CBL protein (p.Ile898Val). This variant is not present in population databases (gnomAD no frequency). 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: 40428). 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 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.
Ambry Genetics RCV004018709 SCV003947783 uncertain significance Cardiovascular phenotype 2023-04-24 criteria provided, single submitter clinical testing The c.2692A>G (p.I898V) alteration is located in exon 16 (coding exon 16) of the CBL gene. This alteration results from a A to G substitution at nucleotide position 2692, causing the isoleucine (I) at amino acid position 898 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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