Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001016108 | SCV001177023 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-08-05 | criteria provided, single submitter | clinical testing | The p.L872P variant (also known as c.2615T>C), located in coding exon 25 of the RB1 gene, results from a T to C substitution at nucleotide position 2615. The leucine at codon 872 is replaced by proline, an amino acid with similar properties. 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. |
| Invitae | RCV001359224 | SCV001555087 | uncertain significance | Retinoblastoma | 2023-07-17 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 872 of the RB1 protein (p.Leu872Pro). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with RB1-related conditions. ClinVar contains an entry for this variant (Variation ID: 821572). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on RB1 protein function. 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. |
| Prevention |
RCV003411950 | SCV004108642 | uncertain significance | RB1-related condition | 2023-04-07 | criteria provided, single submitter | clinical testing | The RB1 c.2615T>C variant is predicted to result in the amino acid substitution p.Leu872Pro. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/13-49050931-T-C) and in ClinVar this variant has been interpreted as uncertain (https://www.ncbi.nlm.nih.gov/clinvar/variation/821572/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |