Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000472528 | SCV000553531 | uncertain significance | DICER1-related tumor predisposition | 2025-01-23 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 1238 of the DICER1 protein (p.Leu1238Pro). This variant is not present in population databases (gnomAD no frequency). 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: 412075). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt DICER1 protein function with a negative predictive value of 95%. 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. |
| Ambry Genetics | RCV001020955 | SCV001182504 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-01 | criteria provided, single submitter | clinical testing | The p.L1238P variant (also known as c.3713T>C), located in coding exon 20 of the DICER1 gene, results from a T to C substitution at nucleotide position 3713. The leucine at codon 1238 is replaced by proline, an amino acid with 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. |
| Baylor Genetics | RCV003470504 | SCV004193320 | uncertain significance | Global developmental delay - lung cysts - overgrowth - Wilms tumor syndrome | 2024-03-22 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV004767278 | SCV005375961 | uncertain significance | not provided | 2023-11-29 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Laboratory of Medical Genetics Unit, |
RCV004776286 | SCV005382020 | uncertain significance | Childhood kidney cell carcinoma; High-grade astrocytoma with piloid features | no assertion criteria provided | research |