Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001016108 | SCV001177023 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-08-22 | 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, 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. |
| Labcorp Genetics |
RCV001359224 | SCV001555087 | likely benign | Retinoblastoma | 2024-12-20 | criteria provided, single submitter | clinical testing | |
| Prevention |
RCV003411950 | SCV004108642 | uncertain significance | RB1-related disorder | 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. |
| Baylor Genetics | RCV004569948 | SCV005054133 | uncertain significance | Malignant tumor of urinary bladder | 2024-02-09 | criteria provided, single submitter | clinical testing | |
| St. |
RCV001359224 | SCV005402279 | uncertain significance | Retinoblastoma | 2024-05-12 | criteria provided, single submitter | clinical testing | The RB1 c.2615T>C (p.Leu872Pro) missense change has a maximum subpopulation frequency of 0.0009% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org). The in silico tool REVEL predicts a deleterious effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in individuals with retinoblastoma. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance. |