Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001222235 | SCV001394329 | uncertain significance | DICER1-related tumor predisposition | 2021-06-15 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine with isoleucine at codon 1492 of the DICER1 protein (p.Met1492Ile). The methionine residue is weakly conserved and there is a small physicochemical difference between methionine and isoleucine. 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 isoleucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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). |
Ambry Genetics | RCV003353217 | SCV004055084 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-09-04 | criteria provided, single submitter | clinical testing | The p.M1492I variant (also known as c.4476G>A), located in coding exon 22 of the DICER1 gene, results from a G to A substitution at nucleotide position 4476. The methionine at codon 1492 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |