Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV000501989 | SCV000595823 | pathogenic | Congenital amegakaryocytic thrombocytopenia | 2016-10-14 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001361128 | SCV001557092 | uncertain significance | Congenital amegakaryocytic thrombocytopenia; Essential thrombocythemia | 2023-06-23 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 14164). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies have shown that this missense change affects MPL function (PMID: 18769448, 28823277, 31294534). 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 individual(s) with essential thrombocythemia and/or myeloproliferative neoplasms (PMID: 20113333, 21326037, 25023898). This variant is present in population databases (rs121913615, gnomAD 0.007%). This sequence change replaces tryptophan, which is neutral and slightly polar, with leucine, which is neutral and non-polar, at codon 515 of the MPL protein (p.Trp515Leu). |
OMIM | RCV000015227 | SCV000035485 | pathogenic | Myelofibrosis with myeloid metaplasia | 2006-11-15 | no assertion criteria provided | literature only | |
OMIM | RCV000022668 | SCV000043957 | pathogenic | Thrombocythemia 2, somatic | 2006-11-15 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000422740 | SCV000505203 | likely pathogenic | Hematologic neoplasm | 2014-12-26 | no assertion criteria provided | literature only |