Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000559948 | SCV000629342 | uncertain significance | Retinoblastoma | 2018-04-20 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine with valine at codon 233 of the RB1 protein (p.Met233Val). The methionine residue is weakly conserved and there is a small physicochemical difference between methionine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with retinoblastoma (Invitae). However, in that individual a pathogenic variant was also identified in RB1, which suggests that this c.697A>G variant was not the primary cause of disease. ClinVar contains an entry for this variant (Variation ID: 458179). 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 valine 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. 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. |