Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002627834 | SCV003501375 | uncertain significance | Retinoblastoma | 2022-06-26 | 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. This variant has not been reported in the literature in individuals affected with RB1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 554 of the RB1 protein (p.Glu554Gly). |
| Ambry Genetics | RCV003294547 | SCV004002004 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-04-06 | criteria provided, single submitter | clinical testing | Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.The p.E554G variant (also known as c.1661A>G), located in coding exon 17 of the RB1 gene, results from an A to G substitution at nucleotide position 1661. The glutamic acid at codon 554 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. |