Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001301473 | SCV001490643 | uncertain significance | Retinoblastoma | 2023-10-03 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 484 of the RB1 protein (p.Met484Thr). This variant is not present in population databases (gnomAD no frequency). 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: 1004720). 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. 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. |
| Ambry Genetics | RCV002393714 | SCV002698195 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-09-05 | criteria provided, single submitter | clinical testing | The p.M484T variant (also known as c.1451T>C), located in coding exon 16 of the RB1 gene, results from a T to C substitution at nucleotide position 1451. The methionine at codon 484 is replaced by threonine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species, and threonine is the reference amino acid in other 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. |