Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001070402 | SCV001235629 | uncertain significance | DICER1-related tumor predisposition | 2023-08-17 | 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. This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1108 of the DICER1 protein (p.Ile1108Val). This variant is present in population databases (rs751551790, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with DICER1-related conditions. ClinVar contains an entry for this variant (Variation ID: 863435). |
Ambry Genetics | RCV003363101 | SCV004054999 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-07-10 | criteria provided, single submitter | clinical testing | The p.I1108V variant (also known as c.3322A>G), located in coding exon 20 of the DICER1 gene, results from an A to G substitution at nucleotide position 3322. The isoleucine at codon 1108 is replaced by valine, 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. |