Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001018735 | SCV001180007 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-10-10 | criteria provided, single submitter | clinical testing | The p.S302F variant (also known as c.905C>T), located in coding exon 9 of the RB1 gene, results from a C to T substitution at nucleotide position 905. The serine at codon 302 is replaced by phenylalanine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. 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. |
| Invitae | RCV002549484 | SCV003474166 | uncertain significance | Retinoblastoma | 2022-02-07 | 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. This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 302 of the RB1 protein (p.Ser302Phe). 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: 822951). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. |