Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001063232 | SCV001228069 | uncertain significance | DICER1-related tumor predisposition | 2023-04-19 | 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. 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: 857537). This variant has not been reported in the literature in individuals affected with DICER1-related conditions. This variant is present in population databases (rs375211466, gnomAD 0.01%). This sequence change replaces leucine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1143 of the DICER1 protein (p.Leu1143Ile). |
| Ambry Genetics | RCV002451271 | SCV002615550 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-06-29 | criteria provided, single submitter | clinical testing | The p.L1143I variant (also known as c.3427C>A), located in coding exon 20 of the DICER1 gene, results from a C to A substitution at nucleotide position 3427. The leucine at codon 1143 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is not 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. |