Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003226763 | SCV003922962 | likely pathogenic | Congenital amegakaryocytic thrombocytopenia | 2023-03-15 | criteria provided, single submitter | clinical testing | Variant summary: MPL c.1145delC (p.Pro382LeufsX114) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic in ClinVar. The variant allele was found at a frequency of 4e-06 in 251482 control chromosomes (gnomAD). To our knowledge, no occurrence of c.1145delC in individuals affected with Congenital Amegakaryocytic Thrombocytopenia and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Invitae | RCV003779815 | SCV004576195 | pathogenic | Congenital amegakaryocytic thrombocytopenia; Essential thrombocythemia | 2023-02-14 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs759135440, gnomAD 0.007%). This sequence change creates a premature translational stop signal (p.Pro382Leufs*114) in the MPL gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MPL are known to be pathogenic (PMID: 8073287, 11133753). This variant has not been reported in the literature in individuals affected with MPL-related conditions. For these reasons, this variant has been classified as Pathogenic. |