Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001039224 | SCV001202742 | pathogenic | DICER1-related tumor predisposition | 2019-06-09 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Pro1336Leufs*11) in the DICER1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with DICER1-related conditions. Loss-of-function variants in DICER1 are known to be pathogenic (PMID: 19556464, 21266384). For these reasons, this variant has been classified as Pathogenic. |
| Foulkes Cancer Genetics LDI, |
RCV001039224 | SCV001372018 | pathogenic | DICER1-related tumor predisposition | 2019-07-01 | criteria provided, single submitter | curation | ACMG criteria met: PVS1, PM2, PP4 |
| Ambry Genetics | RCV002372764 | SCV002625369 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-12-23 | criteria provided, single submitter | clinical testing | The c.4007delC pathogenic mutation, located in coding exon 20 of the DICER1 gene, results from a deletion of one nucleotide at nucleotide position 4007, causing a translational frameshift with a predicted alternate stop codon (p.P1336Lfs*11). This alteration has been identified as a de novo finding in a child with mesenchymal hamartoma of the liver, thyroid nodules and follicular thyroid adenoma (Apellaniz-Ruiz M et al. N Engl J Med, 2019 05;380:1834-1842). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |