Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002050580 | SCV002113555 | uncertain significance | Retinoblastoma | 2023-06-24 | 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 expected to disrupt RB1 protein function. ClinVar contains an entry for this variant (Variation ID: 1347362). 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 leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 647 of the RB1 protein (p.Leu647Pro). |
| Ambry Genetics | RCV002406913 | SCV002719291 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-06-24 | criteria provided, single submitter | clinical testing | The p.L647P variant (also known as c.1940T>C), located in coding exon 19 of the RB1 gene, results from a T to C substitution at nucleotide position 1940. The leucine at codon 647 is replaced by proline, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |