Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001231230 | SCV001403743 | uncertain significance | DICER1-related tumor predisposition | 2023-03-09 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 517 of the DICER1 protein (p.Ile517Leu). This variant is not present in population databases (gnomAD no frequency). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt DICER1 protein function. ClinVar contains an entry for this variant (Variation ID: 958121). This variant has not been reported in the literature in individuals affected with DICER1-related conditions. |
Ambry Genetics | RCV002402723 | SCV002705140 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-11-01 | criteria provided, single submitter | clinical testing | The p.I517L variant (also known as c.1549A>C), located in coding exon 9 of the DICER1 gene, results from an A to C substitution at nucleotide position 1549. The isoleucine at codon 517 is replaced by leucine, 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. |
Baylor Genetics | RCV003462785 | SCV004193455 | uncertain significance | Global developmental delay - lung cysts - overgrowth - Wilms tumor syndrome | 2023-06-19 | criteria provided, single submitter | clinical testing |