Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001978087 | SCV002266502 | uncertain significance | Retinoblastoma | 2023-09-18 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 1476715). This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 402 of the RB1 protein (p.Ser402Phe). 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. 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 | RCV002344154 | SCV002649203 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-05-12 | criteria provided, single submitter | clinical testing | The p.S402F variant (also known as c.1205C>T), located in coding exon 12 of the RB1 gene, results from a C to T substitution at nucleotide position 1205. The serine at codon 402 is replaced by phenylalanine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |