Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001015974 | SCV001176873 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-01-24 | criteria provided, single submitter | clinical testing | The p.D856E variant (also known as c.2568C>A), located in coding exon 25 of the RB1 gene, results from a C to A substitution at nucleotide position 2568. The aspartic acid at codon 856 is replaced by glutamic acid, an amino acid with highly similar properties. This amino acid position is well 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. |
| Invitae | RCV001225078 | SCV001397313 | uncertain significance | Retinoblastoma | 2023-08-08 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). 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. 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 RB1 protein function. ClinVar contains an entry for this variant (Variation ID: 821497). This variant has not been reported in the literature in individuals affected with RB1-related conditions. This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 856 of the RB1 protein (p.Asp856Glu). |