Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002626112 | SCV002960211 | uncertain significance | Retinoblastoma | 2023-01-06 | 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. 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. This variant has not been reported in the literature in individuals affected with RB1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 117 of the RB1 protein (p.Phe117Leu). |
| Ambry Genetics | RCV004673693 | SCV005160566 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-06-04 | criteria provided, single submitter | clinical testing | The p.F117L variant (also known as c.349T>C), located in coding exon 3 of the RB1 gene, results from a T to C substitution at nucleotide position 349. The phenylalanine at codon 117 is replaced by leucine, 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. Based on the available evidence, the clinical significance of this variant remains unclear. |