Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV001195291 | SCV001365602 | likely pathogenic | DICER1-related tumor predisposition | 2019-03-22 | criteria provided, single submitter | clinical testing | The p.Arg1368fs variant in DICER1 has not been previously reported in individuals with DICER1-related disorders and was absent from large population studies. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 1368 and leads to a premature termination codon 8 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Heterozygous loss of function of the DICER1 gene is an established disease mechanism in DICER1-related disorders. In summary, although additional studies are required to fully establish its clinical significance, the p.Arg1368fs variant is likely pathogenic. ACMG/AMP Criteria applied: PVS1; PM2. |
| Invitae | RCV001195291 | SCV002234814 | pathogenic | DICER1-related tumor predisposition | 2021-11-11 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 929949). This variant has not been reported in the literature in individuals affected with DICER1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg1368Profs*8) in the DICER1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DICER1 are known to be pathogenic (PMID: 19556464, 21266384). |