Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001039547 | SCV001203079 | uncertain significance | Retinoblastoma | 2021-07-14 | criteria provided, single submitter | clinical testing | This sequence change affects codon 837 of the RB1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the RB1 protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with RB1-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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. |
| Ambry Genetics | RCV002427496 | SCV002744265 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-11-25 | criteria provided, single submitter | clinical testing | The c.2511A>G variant (also known as p.E837E), located in coding exon 24 of the RB1 gene, results from an A to G substitution at nucleotide position 2511. This nucleotide substitution does not change the glutamic acid at codon 837. However, this change occurs in the base pair of coding exon 24, which makes it likely to have some effect on normal mRNA splicing. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |