Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002035051 | SCV002107666 | uncertain significance | Retinoblastoma | 2020-11-17 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but 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 lysine with arginine at codon 765 of the RB1 protein (p.Lys765Arg). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and arginine. |
| Ambry Genetics | RCV004656669 | SCV005160571 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-06-10 | criteria provided, single submitter | clinical testing | The p.K765R variant (also known as c.2294A>G), located in coding exon 22 of the RB1 gene, results from an A to G substitution at nucleotide position 2294. The lysine at codon 765 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |