Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001321511 | SCV001512343 | uncertain significance | Retinoblastoma | 2020-11-15 | 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 proline with serine at codon 789 of the RB1 protein (p.Pro789Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine. |
| Ambry Genetics | RCV003166864 | SCV003913091 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-11-15 | criteria provided, single submitter | clinical testing | The p.P789S variant (also known as c.2365C>T), located in coding exon 23 of the RB1 gene, results from a C to T substitution at nucleotide position 2365. The proline at codon 789 is replaced by serine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |