ClinVar Miner

Submissions for variant NM_005188.4(CBL):c.1552A>G (p.Thr518Ala)

gnomAD frequency: 0.00001  dbSNP: rs377734587
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000654919 SCV000776825 likely benign RASopathy 2023-09-22 criteria provided, single submitter clinical testing
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV002254706 SCV002525964 uncertain significance CBL-related disorder 2022-02-03 criteria provided, single submitter clinical testing The CBL NM_005188.3 (c.1552A>G; p.Thr518Ala) missense change has a maximum subpopulation frequency of 0.012% in gnomAD v2.1.1 ( https://gnomad.broadinstitute.org/variant/11-119155799-A-G ). Seven of seven in silico tools predict a benign effect of this variant on protein function (BP4), but to our knowledge these predictions have not been confirmed by functional assays. To our knowledge, this variant has not been reported in individuals with Noonan syndrome-like disorders. In summary, this variant meets criteria to be classified as of uncertain significance based on the ACMG/AMP criteria: BP4
Ambry Genetics RCV004025943 SCV005022967 uncertain significance Cardiovascular phenotype 2023-12-25 criteria provided, single submitter clinical testing The p.T518A variant (also known as c.1552A>G), located in coding exon 10 of the CBL gene, results from an A to G substitution at nucleotide position 1552. The threonine at codon 518 is replaced by alanine, 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.

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.