Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000460404 | SCV000551818 | uncertain significance | Retinoblastoma | 2020-10-21 | 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 disease. ClinVar contains an entry for this variant (Variation ID: 410935). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with lysine at codon 492 of the RB1 protein (p.Glu492Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. |
| Ambry Genetics | RCV000492129 | SCV000580839 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-12-31 | criteria provided, single submitter | clinical testing | The p.E492K variant (also known as c.1474G>A), located in coding exon 16 of the RB1 gene, results from a G to A substitution at nucleotide position 1474. The glutamic acid at codon 492 is replaced by lysine, an amino acid with 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |