Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002457608 | SCV002736902 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-09-17 | criteria provided, single submitter | clinical testing | The p.P776A variant (also known as c.2326C>G) is located in coding exon 23 of the RB1 gene. The proline at codon 776 is replaced by alanine, an amino acid with highly similar properties. This change occurs in the first base pair of coding exon 23. This amino acid position is highly conserved in available vertebrate species. 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. |
Labcorp Genetics |
RCV003626789 | SCV004560642 | uncertain significance | Retinoblastoma | 2022-11-25 | 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 proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 776 of the RB1 protein (p.Pro776Ala). |