Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000812984 | SCV000953314 | benign | Retinoblastoma | 2024-12-29 | criteria provided, single submitter | clinical testing | |
| Sema4, |
RCV002255534 | SCV002528292 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-05-20 | criteria provided, single submitter | curation | |
| Ambry Genetics | RCV002255534 | SCV002700350 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-03-15 | criteria provided, single submitter | clinical testing | The p.I470M variant (also known as c.1410T>G), located in coding exon 15 of the RB1 gene, results from a T to G substitution at nucleotide position 1410. The isoleucine at codon 470 is replaced by methionine, an amino acid with highly similar properties. Although this particular variant has not been reported in the literature, a different amino acid change at this same position (p.Ile470Phe) has been reported in two Chinese patients with unilateral retinoblastoma (Li T et al. Int J Clin Exp Pathol 2016;9(2):2120-2126). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Baylor Genetics | RCV003461212 | SCV004208527 | uncertain significance | Malignant tumor of urinary bladder | 2023-07-28 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV000812984 | SCV004844669 | uncertain significance | Retinoblastoma | 2024-09-27 | criteria provided, single submitter | clinical testing | This missense variant replaces isoleucine with methionine at codon 470 of the RB1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with RB1-related disorders in the literature. This variant has been identified in 2/163858 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |