NM_005373.3(MPL):c.1544G>T (p.Trp515Leu) AND Myelofibrosis with myeloid metaplasia

Clinical significance:Pathogenic (Last evaluated: Nov 15, 2006)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000015227.5

Allele description [Variation Report for NM_005373.3(MPL):c.1544G>T (p.Trp515Leu)]

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

Gene:
MPL:MPL proto-oncogene, thrombopoietin receptor [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1p34.2
Genomic location:
Preferred name:
NM_005373.3(MPL):c.1544G>T (p.Trp515Leu)
HGVS:
  • NC_000001.11:g.43349338G>T
  • NG_007525.1:g.16535G>T
  • NM_005373.2:c.1544G>T
  • NM_005373.3:c.1544G>TMANE SELECT
  • NP_005364.1:p.Trp515Leu
  • NP_005364.1:p.Trp515Leu
  • LRG_510t1:c.1544G>T
  • LRG_510:g.16535G>T
  • LRG_510p1:p.Trp515Leu
  • NC_000001.10:g.43815009G>T
  • P40238:p.Trp515Leu
Protein change:
W515L; TRP515LEU
Links:
UniProtKB: P40238#VAR_067561; OMIM: 159530.0011; dbSNP: rs121913615
NCBI 1000 Genomes Browser:
rs121913615
Molecular consequence:
  • NM_005373.2:c.1544G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_005373.3:c.1544G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Myelofibrosis with myeloid metaplasia (MMM)
Synonyms:
Myelofibrosis with myeloid metaplasia, somatic
Identifiers:
MONDO: MONDO:0009692; MedGen: C0026987

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000035485OMIMno assertion criteria providedPathogenic
(Nov 15, 2006)
somaticliterature only

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedsomaticnot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia.

Pikman Y, Lee BH, Mercher T, McDowell E, Ebert BL, Gozo M, Cuker A, Wernig G, Moore S, Galinsky I, DeAngelo DJ, Clark JJ, Lee SJ, Golub TR, Wadleigh M, Gilliland DG, Levine RL.

PLoS Med. 2006 Jul;3(7):e270.

PubMed [citation]
PMID:
16834459
PMCID:
PMC1502153

MPL515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients.

Pardanani AD, Levine RL, Lasho T, Pikman Y, Mesa RA, Wadleigh M, Steensma DP, Elliott MA, Wolanskyj AP, Hogan WJ, McClure RF, Litzow MR, Gilliland DG, Tefferi A.

Blood. 2006 Nov 15;108(10):3472-6. Epub 2006 Jul 25.

PubMed [citation]
PMID:
16868251

Details of each submission

From OMIM, SCV000035485.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)

Description

Pikman et al. (2006) identified a somatic 1544G-T transversion in the MPL gene, resulting in a trp515-to-leu (W515L) substitution, in 4 (9%) of 45 patients with myelofibrosis with myeloid metaplasia (see 254450). Two of the patients also had leukocytosis and thrombocytosis at the time of disease presentation. Functional expression studies showed that this was an activating mutation conferring cytokine-independent growth and hypersensitivity to TPHO in cell culture. The W515L mutant protein resulted in constitutive phosphorylation of downstream signaling molecules, including JAK2 (147796), STAT3 (102582), and ERK (600997). Expression of W515L in murine bone marrow resulted in a fully penetrant myeloproliferative disorder with thrombocytosis and extramedullary hematopoiesis.

Pardanani et al. (2006) identified a somatic W515L mutation in 9 patients with myelofibrosis with myeloid metaplasia and in 4 with essential thrombocythemia (601977). Six of these patients were also heterozygous for the JAK2 V617F mutation (147796.0001), 2 of whom also carried the MPL W515K mutation (159530.0012)

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1somaticnot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 20, 2021

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