ClinVar Miner

Submissions for variant NM_005188.4(CBL):c.1423G>A (p.Gly475Ser)

gnomAD frequency: 0.00006  dbSNP: rs764599897
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
Labcorp Genetics (formerly Invitae), Labcorp RCV000542936 SCV000659096 likely benign RASopathy 2023-04-04 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001532911 SCV001748711 uncertain significance not specified 2023-05-30 criteria provided, single submitter clinical testing Variant summary: CBL c.1423G>A (p.Gly475Ser) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 250944 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1423G>A in individuals affected with Noonan Syndrome-Like Disorder and no experimental evidence demonstrating its impact on protein function have been reported. The following publications have been ascertained in the context of this evaluation (PMID: 27069254, 25224413, 19387008, 23690417, 21828135, 19901108, 20619386, 25952305, 20951944, 19620960, 22733026, 23010802, 29296819). Two ClinVar submitters have assessed the variant since 2014: one classified the variant as likely benign, and one as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Fulgent Genetics, Fulgent Genetics RCV002483510 SCV002787783 uncertain significance Juvenile myelomonocytic leukemia; CBL-related disorder 2021-12-03 criteria provided, single submitter clinical testing
Ambry Genetics RCV004992356 SCV005545748 uncertain significance Cardiovascular phenotype 2024-09-17 criteria provided, single submitter clinical testing The p.G475S variant (also known as c.1423G>A), located in coding exon 9 of the CBL gene, results from a G to A substitution at nucleotide position 1423. The glycine at codon 475 is replaced by serine, an amino acid with similar properties. This variant was reported in a subject with features of Noonan syndrome, but was also seen in an unaffected parent (Martinelli S et al. Hum Mutat, 2015 Aug;36:787-96). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant 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.