Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000801034 | SCV000940786 | uncertain significance | Retinoblastoma | 2019-05-27 | criteria provided, single submitter | clinical testing | 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 variant has not been reported in the literature in individuals with RB1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces phenylalanine with serine at codon 131 of the RB1 protein (p.Phe131Ser). The phenylalanine residue is highly conserved and there is a large physicochemical difference between phenylalanine and serine. |
| Ambry Genetics | RCV003307459 | SCV004001595 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-04-07 | criteria provided, single submitter | clinical testing | The p.F131S variant (also known as c.392T>C), located in coding exon 4 of the RB1 gene, results from a T to C substitution at nucleotide position 392. The phenylalanine at codon 131 is replaced by serine, an amino acid with highly dissimilar properties. This amino acid position is conserved. 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. |