Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000822868 | SCV000963690 | uncertain significance | Retinoblastoma | 2024-09-09 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 459 of the RB1 protein (p.Ser459Phe). This variant is not present in population databases (gnomAD no frequency). 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: 664716). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on RB1 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 | RCV001011230 | SCV001171528 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-04-30 | criteria provided, single submitter | clinical testing | The p.S459F variant (also known as c.1376C>T), located in coding exon 14 of the RB1 gene, results from a C to T substitution at nucleotide position 1376. The serine at codon 459 is replaced by phenylalanine, an amino acid with highly dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |
| Fulgent Genetics, |
RCV002487851 | SCV002784398 | uncertain significance | Bone osteosarcoma; Malignant tumor of urinary bladder; Small cell lung carcinoma; Retinoblastoma | 2022-05-24 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV000822868 | SCV004831281 | uncertain significance | Retinoblastoma | 2023-04-27 | criteria provided, single submitter | clinical testing |