ClinVar Miner

Submissions for variant NM_005373.2(MPL):c.1544G>T (p.Trp515Leu) (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 thrombocytemia 2020-05-06 criteria provided, single submitter clinical testing This sequence change replaces tryptophan with leucine at codon 515 of the MPL protein (p.Trp515Leu). The tryptophan residue is weakly conserved and there is a small physicochemical difference between tryptophan and leucine. This variant is present in population databases (rs121913615, ExAC 0.01%). This variant has been observed as a somatic change in individuals with essential thrombocythemia and/or myeloproliferative neoplasms (PMID: 25023898, 20113333, 21326037), but has not been identified as a germline change in affected individuals. ClinVar contains an entry for this variant (Variation ID: 14164). This variant has been reported to affect MPL protein function (PMID: 31294534, 18769448, 28823277). 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.
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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