Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000632962 | SCV000754171 | uncertain significance | Retinoblastoma | 2023-12-13 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 365 of the RB1 protein (p.Glu365Gln). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with RB1-related conditions. ClinVar contains an entry for this variant (Variation ID: 527932). 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 with a negative predictive value of 80%. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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 | RCV002448949 | SCV002734406 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-01 | criteria provided, single submitter | clinical testing | The p.E365Q variant (also known as c.1093G>C), located in coding exon 11 of the RB1 gene, results from a G to C substitution at nucleotide position 1093. The glutamic acid at codon 365 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Baylor Genetics | RCV003459513 | SCV004208542 | uncertain significance | Malignant tumor of urinary bladder | 2023-06-02 | criteria provided, single submitter | clinical testing |