ClinVar Miner

Submissions for variant NM_005188.4(CBL):c.2678G>A (p.Arg893Gln)

gnomAD frequency: 0.00002  dbSNP: rs751198294
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000593423 SCV000709716 uncertain significance not specified 2018-02-28 criteria provided, single submitter clinical testing Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: GnomAd 11:119170448 G / A: East Asian 1/1618; well conserved; Not in ClinVar, Pubmed, Google search or HGMD; probably damaging by polyphen
Illumina Laboratory Services, Illumina RCV001103085 SCV001259803 uncertain significance CBL-related disorder 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae RCV001303309 SCV001492550 uncertain significance RASopathy 2023-11-20 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 893 of the CBL protein (p.Arg893Gln). This variant is present in population databases (rs751198294, gnomAD 0.06%). 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: 503535). 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.
GeneDx RCV003222055 SCV003918541 uncertain significance not provided 2022-10-11 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Located in the Interaction with CD2AP and Ubiquitin-Associated and Leucine Zipper domains (Martinelli et al., 2010; Kirsch et al., 2001); Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 20619386, 11067845)

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