Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000559312 | SCV000629322 | uncertain significance | Retinoblastoma | 2017-03-19 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with glycine at codon 919 of the RB1 protein (p.Ser919Gly). The serine residue is moderately conserved and there is a small physicochemical difference between serine and glycine. In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. 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. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a RB1-related disease. |
| Ambry Genetics | RCV002438314 | SCV002751944 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-10-13 | criteria provided, single submitter | clinical testing | The p.S919G variant (also known as c.2755A>G), located in coding exon 27 of the RB1 gene, results from an A to G substitution at nucleotide position 2755. The serine at codon 919 is replaced by glycine, an amino acid with similar properties. This amino acid position is not well conserved in available 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. |