Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003815415 | SCV004609303 | pathogenic | Congenital amegakaryocytic thrombocytopenia; Essential thrombocythemia | 2023-07-25 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Pro136 amino acid residue in MPL. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16470591, 18422784, 27100302, 32703794). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this missense change affects MPL function (PMID: 24438083). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MPL protein function. This missense change has been observed in individuals with autosomal recessive congenital amegakaryocytic thrombocytopenia (PMID: 16470591, 27100302, 32703794). This variant is present in population databases (no rsID available, gnomAD 0.002%). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 136 of the MPL protein (p.Pro136Leu). |