Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000597829 | SCV000709715 | uncertain significance | not specified | 2018-02-28 | criteria provided, single submitter | clinical testing | Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: GnomAd 11:119170384 C / A: Europeans 5/111684; fairly- well conserved, but lysine seen in cavefish; Not in ClinVar, Pubmed, Google search or HGMD; possibly damaging by polyphen |
| Invitae | RCV001047665 | SCV001211636 | uncertain significance | RASopathy | 2023-07-13 | criteria provided, single submitter | clinical testing | 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. This missense change has been observed in individual(s) with acute lymphoblastic leukemia (PMID: 31102422). This sequence change replaces glutamine, which is neutral and polar, with lysine, which is basic and polar, at codon 872 of the CBL protein (p.Gln872Lys). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. ClinVar contains an entry for this variant (Variation ID: 503534). 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 not expected to disrupt CBL protein function. |
| Gene |
RCV001823150 | SCV002072672 | uncertain significance | not provided | 2022-01-19 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Observed in an individual with childhood acute lymphoblastic leukemia (de Smith 2019); This variant is associated with the following publications: (PMID: 31102422) |
| Ambry Genetics | RCV003160065 | SCV003855260 | uncertain significance | Cardiovascular phenotype | 2023-02-12 | criteria provided, single submitter | clinical testing | The p.Q872K variant (also known as c.2614C>A), located in coding exon 16 of the CBL gene, results from a C to A substitution at nucleotide position 2614. The glutamine at codon 872 is replaced by lysine, an amino acid with similar properties. This variant has been reported in 1/1120 pediatric cancer patients who underwent whole genome sequencing and/or whole exome sequencing; this patient was diagnosed with acute lymphocytic leukemia (ALL) (Zhang J et al. N Engl J Med, 2015 Dec;373:2336-2346). Additionally, this alteration was reported as a putative germline alteration of interest identified in 1/57 HD-ALL patients from the California Childhood Leukemia study who were tested via targeted multi-gene panel testing. (de Smith AJ et al. Genes Chromosomes Cancer, 2019 Oct;58:723-730). This amino acid position is highly conserved in available vertebrate species. 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. |