ClinVar Miner

Submissions for variant NM_005373.3(MPL):c.1544G>T (p.Trp515Leu)

gnomAD frequency: 0.00001  dbSNP: rs121913615
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago 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 (DoCM) RCV000422740 SCV000505203 likely pathogenic Hematologic neoplasm 2014-12-26 no assertion criteria provided literature only

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