Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001206402 | SCV001377710 | uncertain significance | Retinoblastoma | 2019-09-26 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). This variant has not been reported in the literature in individuals with RB1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with methionine at codon 409 of the RB1 protein (p.Val409Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. |
| Ambry Genetics | RCV002365932 | SCV002660927 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-07-03 | criteria provided, single submitter | clinical testing | The p.V409M variant (also known as c.1225G>A), located in coding exon 13 of the RB1 gene, results from a G to A substitution at nucleotide position 1225. The valine at codon 409 is replaced by methionine, an amino acid with highly similar 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. |