Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001969599 | SCV002265179 | uncertain significance | Retinoblastoma | 2020-11-12 | 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 tolerated, 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 threonine with asparagine at codon 633 of the RB1 protein (p.Thr633Asn). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and asparagine. |
| Ambry Genetics | RCV003170289 | SCV003854403 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-12-19 | criteria provided, single submitter | clinical testing | The p.T633N variant (also known as c.1898C>A), located in coding exon 19 of the RB1 gene, results from a C to A substitution at nucleotide position 1898. The threonine at codon 633 is replaced by asparagine, an amino acid with 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. |