Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001016265 | SCV001177202 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-02-26 | criteria provided, single submitter | clinical testing | The p.G89E variant (also known as c.266G>A), located in coding exon 3 of the RB1 gene, results from a G to A substitution at nucleotide position 266. The glycine at codon 89 is replaced by glutamic acid, an amino acid with very few similar properties. This amino acid position is not well conserved in available vertebrate species with glutamic acid being the reference amino acid in many vertebrate species. 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. |
| Labcorp Genetics |
RCV001873275 | SCV002248312 | uncertain significance | Retinoblastoma | 2020-11-10 | 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 glutamic acid 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. ClinVar contains an entry for this variant (Variation ID: 821651). This variant is present in population databases (rs371655281, ExAC 0.002%). This sequence change replaces glycine with glutamic acid at codon 89 of the RB1 protein (p.Gly89Glu). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and glutamic acid. |
| Baylor Genetics | RCV004569951 | SCV005054126 | uncertain significance | Malignant tumor of urinary bladder | 2024-02-23 | criteria provided, single submitter | clinical testing |