Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001206258 | SCV001377556 | uncertain significance | DICER1-related tumor predisposition | 2022-08-18 | 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. ClinVar contains an entry for this variant (Variation ID: 937280). 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 asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 1186 of the DICER1 protein (p.Asn1186Asp). |
| Ambry Genetics | RCV002339524 | SCV002618766 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-11-07 | criteria provided, single submitter | clinical testing | The p.N1186D variant (also known as c.3556A>G), located in coding exon 20 of the DICER1 gene, results from an A to G substitution at nucleotide position 3556. The asparagine at codon 1186 is replaced by aspartic acid, 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. |