Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001016760 | SCV001177753 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-10-22 | criteria provided, single submitter | clinical testing | The p.R95K variant (also known as c.284G>A), located in coding exon 2 of the DICER1 gene, results from a G to A substitution at nucleotide position 284. The arginine at codon 95 is replaced by lysine, an amino acid with highly similar properties. This amino acid position is highly conserved in available 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. |
| Invitae | RCV001240701 | SCV001413670 | uncertain significance | DICER1-related tumor predisposition | 2021-02-23 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with DICER1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with lysine at codon 95 of the DICER1 protein (p.Arg95Lys). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and lysine. |