NM_005373.3(MPL):c.1069C>T (p.Arg357Ter) AND Congenital amegakaryocytic thrombocytopenia

Clinical significance:Pathogenic (Last evaluated: Apr 29, 2021)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001420932.1

Allele description [Variation Report for NM_005373.3(MPL):c.1069C>T (p.Arg357Ter)]

NM_005373.3(MPL):c.1069C>T (p.Arg357Ter)

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.1069C>T (p.Arg357Ter)
HGVS:
  • NC_000001.11:g.43346533C>T
  • NG_007525.1:g.13730C>T
  • NM_005373.2:c.1069C>T
  • NM_005373.3:c.1069C>TMANE SELECT
  • NP_005364.1:p.Arg357Ter
  • NP_005364.1:p.Arg357Ter
  • LRG_510t1:c.1069C>T
  • LRG_510:g.13730C>T
  • LRG_510p1:p.Arg357Ter
  • NC_000001.10:g.43812204C>T
Protein change:
R357*
Links:
dbSNP: rs751975712
NCBI 1000 Genomes Browser:
rs751975712
Molecular consequence:
  • NM_005373.2:c.1069C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_005373.3:c.1069C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Congenital amegakaryocytic thrombocytopenia (CAMT)
Identifiers:
MONDO: MONDO:0011469; MedGen: C1327915; Orphanet: 3319; OMIM: 604498

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001623391Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Pathogenic
(Apr 29, 2021)
germlineclinical testing

PubMed (5)
[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

Pathogenic Germline Variants in 10,389 Adult Cancers.

Huang KL, Mashl RJ, Wu Y, Ritter DI, Wang J, Oh C, Paczkowska M, Reynolds S, Wyczalkowski MA, Oak N, Scott AD, Krassowski M, Cherniack AD, Houlahan KE, Jayasinghe R, Wang LB, Zhou DC, Liu D, Cao S, Kim YW, Koire A, McMichael JF, et al.

Cell. 2018 Apr 5;173(2):355-370.e14. doi: 10.1016/j.cell.2018.03.039.

PubMed [citation]
PMID:
29625052
PMCID:
PMC5949147

Targeted next generation sequencing can serve as an alternative to conventional tests in myeloid neoplasms.

Kim B, Lee H, Jang J, Kim SJ, Lee ST, Cheong JW, Lyu CJ, Min YH, Choi JR.

PLoS One. 2019;14(3):e0212228. doi: 10.1371/journal.pone.0212228.

PubMed [citation]
PMID:
30840646
PMCID:
PMC6402635
See all PubMed Citations (5)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001623391.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

Variant summary: MPL c.1069C>T (p.Arg357X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 1.6e-05 in 251476 control chromosomes. c.1069C>T has been reported in the literature in individuals affected with Congenital Amegakaryocytic Thrombocytopenia (e.g. Chung_2011, Liu_2018, Germeshausen_2020). These data indicate that the variant is likely associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One other clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and cited the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

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

Last Updated: Nov 27, 2021

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