ClinVar Miner

Submissions for variant NM_005188.4(CBL):c.2062C>T (p.Pro688Ser)

gnomAD frequency: 0.00001  dbSNP: rs730880428
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001704137 SCV000207783 likely benign not provided 2020-06-04 criteria provided, single submitter clinical testing In silico analysis supports 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 RCV001308075 SCV001497510 uncertain significance RASopathy 2024-11-03 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 688 of the CBL protein (p.Pro688Ser). This variant is present in population databases (rs730880428, gnomAD 0.002%). 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: 180810). 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.
Ambry Genetics RCV002415688 SCV002724844 uncertain significance Cardiovascular phenotype 2024-11-23 criteria provided, single submitter clinical testing The p.P688S variant (also known as c.2062C>T), located in coding exon 13 of the CBL gene, results from a C to T substitution at nucleotide position 2062. The proline at codon 688 is replaced by serine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV005055079 SCV005689391 uncertain significance CBL-related disorder 2024-11-21 criteria provided, single submitter clinical testing The CBL c.2062C>T (p.Pro688Ser) missense change has a maximum subpopulation frequency of 0.0023% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a benign effect on protein function, but this prediction has not been confirmed by functional studies. This variant has not been reported in the literature in individuals with Noonan syndrome-like. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.