Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001220733 | SCV001392742 | uncertain significance | DICER1-related tumor predisposition | 2022-08-09 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with DICER1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 521 of the DICER1 protein (p.Ile521Val). ClinVar contains an entry for this variant (Variation ID: 949297). 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. |
| Ambry Genetics | RCV002402668 | SCV002708905 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-08-09 | criteria provided, single submitter | clinical testing | The p.I521V variant (also known as c.1561A>G), located in coding exon 9 of the DICER1 gene, results from an A to G substitution at nucleotide position 1561. The isoleucine at codon 521 is replaced by valine, an amino acid with highly similar properties. This amino acid position is well 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. |
| Baylor Genetics | RCV003462751 | SCV004193396 | uncertain significance | Global developmental delay - lung cysts - overgrowth - Wilms tumor syndrome | 2023-08-23 | criteria provided, single submitter | clinical testing |