NM_005373.3(MPL):c.127C>T (p.Arg43Ter) AND MPL-Related Disorders

Clinical significance:Pathogenic (Last evaluated: Oct 4, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000778238.1

Allele description [Variation Report for NM_005373.3(MPL):c.127C>T (p.Arg43Ter)]

NM_005373.3(MPL):c.127C>T (p.Arg43Ter)

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.127C>T (p.Arg43Ter)
HGVS:
  • NC_000001.11:g.43338146C>T
  • NG_007525.1:g.5343C>T
  • NM_005373.2:c.127C>T
  • NM_005373.3:c.127C>TMANE SELECT
  • NP_005364.1:p.Arg43Ter
  • NP_005364.1:p.Arg43Ter
  • LRG_510t1:c.127C>T
  • LRG_510:g.5343C>T
  • LRG_510p1:p.Arg43Ter
  • NC_000001.10:g.43803817C>T
Protein change:
R43*
Links:
dbSNP: rs148434485
NCBI 1000 Genomes Browser:
rs148434485
Molecular consequence:
  • NM_005373.2:c.127C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_005373.3:c.127C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
MPL-Related Disorders
Identifiers:

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000914406Illumina Clinical Services Laboratory,Illuminacriteria provided, single submitter
Pathogenic
(Oct 4, 2018)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

MPL mutations in 23 patients suffering from congenital amegakaryocytic thrombocytopenia: the type of mutation predicts the course of the disease.

Germeshausen M, Ballmaier M, Welte K.

Hum Mutat. 2006 Mar;27(3):296.

PubMed [citation]
PMID:
16470591

Congenital amegakaryocytic thrombocytopenia: clinical and biological consequences of five novel mutations.

Savoia A, Dufour C, Locatelli F, Noris P, Ambaglio C, Rosti V, Zecca M, Ferrari S, di Bari F, Corcione A, Di Stazio M, Seri M, Balduini CL.

Haematologica. 2007 Sep;92(9):1186-93. Epub 2007 Aug 1.

PubMed [citation]
PMID:
17666371
See all PubMed Citations (3)

Details of each submission

From Illumina Clinical Services Laboratory,Illumina, SCV000914406.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

The MPL c.127C>T (p.Arg43Ter) variant is a stop-gained variant predicted to result in premature termination of the protein. The variant has been reported in three studies in which it is identified in a total of six individuals with congenital amegakaryocytic thrombocytopenia, all with a severe phenotype, in one individual in a compound heterozygous state and in five individuals in a homozygous state (Ballmaier et al. 2001; Germeshausen et al. 2006; Savoia et al. 2007). The p.Arg43Ter variant has not been reported in individuals with essential thrombocythemia. The p.Arg43Ter variant was absent from 50 controls and is reported at a frequency of 0.000041 in the total population of the Exome Aggregation Consortium. Savoia et al. (2007) demonstrated that platelet surface expression of other glycoproteins was normal in one individual carrying the variant but MPL expression was scarcely detectable. Serum TPO levels were elevated and in colony-forming unit assays, platelet c-MPL and bone marrow colonies were reduced. Based on the evidence and potential impact of stop-gained variants, the p.Arg43Ter variant is classified as pathogenic for MPL-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.

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

Last Updated: Nov 20, 2021

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