Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV001112571 | SCV001270242 | uncertain significance | Retinoblastoma | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
| Labcorp Genetics |
RCV001112571 | SCV003480530 | uncertain significance | Retinoblastoma | 2023-05-09 | criteria provided, single submitter | clinical testing | 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. 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) performed at Invitae indicates that this missense variant is expected to disrupt RB1 protein function. ClinVar contains an entry for this variant (Variation ID: 882692). This variant has not been reported in the literature in individuals affected with RB1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 666 of the RB1 protein (p.Cys666Arg). |
| Ambry Genetics | RCV003163262 | SCV003871141 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-11-03 | criteria provided, single submitter | clinical testing | The p.C666R variant (also known as c.1996T>C), located in coding exon 20 of the RB1 gene, results from a T to C substitution at nucleotide position 1996. The cysteine at codon 666 is replaced by arginine, an amino acid with highly dissimilar properties. This amino acid position is well 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. |
| All of Us Research Program, |
RCV001112571 | SCV004828909 | uncertain significance | Retinoblastoma | 2023-06-27 | criteria provided, single submitter | clinical testing |