Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Baylor Genetics | RCV001788957 | SCV002030172 | uncertain significance | Juvenile myelomonocytic leukemia | 2021-10-26 | criteria provided, single submitter | clinical testing | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. |
| Gene |
RCV002290763 | SCV002578784 | uncertain significance | not provided | 2022-04-06 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 35236052, 25510280, 20619386, 22315494, 22131879, 25952305, 20880116, 34026204, 22733026, 20644105, 23823657) |
| Labcorp Genetics |
RCV003772177 | SCV004686106 | uncertain significance | RASopathy | 2023-10-03 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 418 of the CBL protein (p.Phe418Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with neutrophilic dermatosis (PMID: 23823657). ClinVar contains an entry for this variant (Variation ID: 1327077). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CBL protein function. 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 | RCV004040834 | SCV005022931 | uncertain significance | Cardiovascular phenotype | 2023-09-25 | criteria provided, single submitter | clinical testing | The p.F418S variant (also known as c.1253T>C), located in coding exon 9 of the CBL gene, results from a T to C substitution at nucleotide position 1253. The phenylalanine at codon 418 is replaced by serine, an amino acid with highly dissimilar properties. This variant has been detected in individuals with hematological disorders or myelodysplastic/myeloproliferative neoplasms (Kohlmann A et al. J Clin Oncol, 2010 Aug;28:3858-65; Adélaïde J et al. Leukemia, 2010 Aug;24:1539-41; Kao HW et al. Neoplasia, 2011 Nov;13:1035-42; Schnittger S et al. Haematologica, 2012 Dec;97:1890-4; Bogucka-Fedorczuk A et al. Cent Eur J Immunol, 2021 Apr;46:121-126). This variant was detected homozygous in peripheral blood cells and neutrophils infiltrating a cutaneous lesion, and heterozygous in fibroblasts from an individual with growth delay and dysmorphic features who developed neutrophilic dermatosis; the proband's mother and sibling were heterozygous for the variant in peripheral blood and were not indicated as affected (Strullu M et al. Leukemia, 2013 Dec;27:2404-7). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |