Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001011902 | SCV001172284 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-11-07 | criteria provided, single submitter | clinical testing | The c.1498A>C variant (also known as p.R500R), located in coding exon 16 of the RB1 gene, results from an A to C substitution at nucleotide position 1498. This nucleotide substitution does not change the at codon 500. However, this change occurs in the last base pair of coding exon 16, which makes it likely to have some effect on normal mRNA splicing. This nucleotide position is well conserved in available vertebrate species. This alteration does not have any significant effect on the native donor splice site using the BDGP and HSF splice site prediction tools, and ESEfinder predicts only a slight weakening of the native donor splice site (Desmet FO et al. Nucleic Acids Res. 2009 May;37:e67). RNA studies on a patient with sporadic bilateral retinoblastoma who carried this alteration showed skipping of exon 16 (Dundar M et al. Proc. Natl. Sci. Counc. Repub. China B 2001 Jul;25(3):166-73). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV003514454 | SCV004297223 | uncertain significance | Retinoblastoma | 2024-01-18 | criteria provided, single submitter | clinical testing | This sequence change affects codon 500 of the RB1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the RB1 protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with retinoblastoma (PMID: 11480772). This variant is also known as R507R (1636A>C). ClinVar contains an entry for this variant (Variation ID: 819383). Studies have shown that this variant is associated with inconclusive levels of altered splicing (PMID: 11480772; Invitae). 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. |