Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000542936 | SCV000659096 | likely benign | RASopathy | 2023-04-04 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
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, |
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. |