Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001015955 | SCV001176850 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-04-14 | criteria provided, single submitter | clinical testing | The p.C853G variant (also known as c.2557T>G), located in coding exon 25 of the RB1 gene, results from a T to G substitution at nucleotide position 2557. The cysteine at codon 853 is replaced by glycine, an amino acid with highly dissimilar properties. This alteration was detected in a cohort of unrelated Brazilian individuals with breast cancer (Sandoval RL et al. PLoS One, 2021 Feb;16:e0247363).This amino acid position is 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. |
| Invitae | RCV003514456 | SCV004268135 | uncertain significance | Retinoblastoma | 2022-11-13 | 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 not expected to disrupt RB1 protein function. ClinVar contains an entry for this variant (Variation ID: 821488). 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 glycine, which is neutral and non-polar, at codon 853 of the RB1 protein (p.Cys853Gly). |