Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001314108 | SCV001504624 | uncertain significance | Retinoblastoma | 2020-11-06 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid with glycine at codon 287 of the RB1 protein (p.Glu287Gly). The glutamic acid residue is highly conserved and there is a moderate physicochemical difference between glutamic acid and glycine. 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 sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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). |
Ambry Genetics | RCV004034308 | SCV005034607 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-11-08 | criteria provided, single submitter | clinical testing | The p.E287G variant (also known as c.860A>G), located in coding exon 8 of the RB1 gene, results from an A to G substitution at nucleotide position 860. The glutamic acid at codon 287 is replaced by glycine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |