Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001224305 | SCV001396494 | uncertain significance | Retinoblastoma | 2021-03-13 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with RB1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with leucine at codon 193 of the RB1 protein (p.Val193Leu). The valine residue is moderately conserved and there is a small physicochemical difference between valine and leucine. |
| Ambry Genetics | RCV002356953 | SCV002652141 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-06-05 | criteria provided, single submitter | clinical testing | The p.V193L variant (also known as c.577G>C), located in coding exon 6 of the RB1 gene, results from a G to C substitution at nucleotide position 577. The valine at codon 193 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |