Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| 3billion | RCV002250838 | SCV002520954 | likely pathogenic | Congenital amegakaryocytic thrombocytopenia | 2022-05-22 | criteria provided, single submitter | clinical testing | The variant is not observed in the gnomAD v2.1.1 dataset. Frameshift: predicted to result in a loss or disruption of normal protein function through protein truncation. The predicted truncated protein may be shortened by more than 10%. Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline. |
| Invitae | RCV003774729 | SCV004595126 | pathogenic | Congenital amegakaryocytic thrombocytopenia; Essential thrombocythemia | 2022-12-24 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Asp558Argfs*4) in the MPL gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 78 amino acid(s) of the MPL protein. For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the MPL protein in which other variant(s) (p.Pro635Leu) have been determined to be pathogenic (PMID: 10971406, 11071383, 18422784). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 1687156). This variant has not been reported in the literature in individuals affected with MPL-related conditions. This variant is not present in population databases (gnomAD no frequency). |