Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001044530 | SCV001208332 | uncertain significance | RASopathy | 2024-10-05 | criteria provided, single submitter | clinical testing | This variant, c.2396_2398del, results in the deletion of 1 amino acid(s) of the CBL protein (p.Ser799del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs755938138, gnomAD 0.006%). 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: 842157). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. |
Institute of Human Genetics, |
RCV004584417 | SCV002578066 | uncertain significance | See cases | 2021-05-05 | criteria provided, single submitter | clinical testing | ACMG categories: PM2 |
Fulgent Genetics, |
RCV002505574 | SCV002814396 | uncertain significance | Juvenile myelomonocytic leukemia; CBL-related disorder | 2021-08-03 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003331031 | SCV004039538 | uncertain significance | not specified | 2023-08-15 | criteria provided, single submitter | clinical testing | Variant summary: CBL c.2396_2398delCCT (p.Ser799del) results in an in-frame deletion that is predicted to remove one amino acid from the encoded protein. The variant allele was found at a frequency of 2.8e-05 in 251472 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.2396_2398delCCT in individuals affected with Noonan Syndrome and Related Conditions and no experimental evidence demonstrating its impact on protein function have been reported. Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |