ClinVar Miner

Submissions for variant NM_005373.3(MPL):c.235_236del (p.Leu79fs)

gnomAD frequency: 0.00005  dbSNP: rs587778514
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000503692 SCV000595824 pathogenic Congenital amegakaryocytic thrombocytopenia 2017-04-18 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000503692 SCV000698584 pathogenic Congenital amegakaryocytic thrombocytopenia 2017-01-12 criteria provided, single submitter clinical testing Variant summary: The MPL c.235_236delCT (p.Leu79Glufs) variant results in a premature termination codon, predicted to cause a truncated or absent MPL protein due to nonsense mediated decay, which are commonly known mechanisms for disease. One in silico tool predicts a damaging outcome for this variant. This variant was found in 6/121376 control chromosomes at a frequency of 0.0000494, which does not exceed the estimated maximal expected allele frequency of a pathogenic MPL variant (0.002357). The variant has been reported in affected individuals in the literature in the homozygous and compound heterozygous state. Taken together, this variant is classified as pathogenic.
Invitae RCV000818190 SCV000958789 pathogenic Congenital amegakaryocytic thrombocytopenia; Essential thrombocythemia 2024-01-29 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu79Glufs*84) in the MPL gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MPL are known to be pathogenic (PMID: 8073287, 11133753). This variant is present in population databases (rs587778514, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with congenital amegakaryocytic thrombocytopenia (PMID: 11133753, 17666371). This variant is also known as del235/236. ClinVar contains an entry for this variant (Variation ID: 134822). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV002281948 SCV002571542 pathogenic not provided 2022-09-04 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Published functional studies demonstrate a damaging effect of no protein expression (Gandhi et al., 2005); This variant is associated with the following publications: (PMID: 19388932, 17666371, 21228398, 16470591, 19302922, 31350202, 29625052, 34426522, 31589614, 11133753, 16219544)
Fulgent Genetics, Fulgent Genetics RCV002498569 SCV002810459 pathogenic Congenital amegakaryocytic thrombocytopenia; Primary myelofibrosis; Thrombocythemia 2 2022-05-02 criteria provided, single submitter clinical testing
Neuberg Centre For Genomic Medicine, NCGM RCV000503692 SCV004047070 pathogenic Congenital amegakaryocytic thrombocytopenia criteria provided, single submitter clinical testing The MPL c.235_236del (p.Leu79GlufsTer84) variant has been reported in homozygous state in individuals affected with Amegakaryocytic Thrombocytopenia, Congenital (Ballmaier M et al.). Experimental studies have shown that this frameshift predicted to result in a complete absence of functional c-Mpl protein. This variant has also been reported to lead to a complete loss of a functional TPO receptor c-Mpl (Ballmaier M et al.). This variant has been submitted with the allele frequency 0.005% in the gnomAD and novel in 1000 genome database. It has been submitted to ClinVar as Pathogenic. This variant causes a frameshift starting with codon Leucine 79, changes this amino acid to Glutamic Acid residue, and creates a premature Stop codon at position 84 of the new reading frame, denoted p.Leu79GlufsTer84. Loss-of-function variants in MPL are known to be pathogenic (Gurney AL et al.) For these reasons, this variant has been classified as Pathogenic.
ITMI RCV000121536 SCV000085730 not provided not specified 2013-09-19 no assertion provided reference population
Natera, Inc. RCV000503692 SCV001453969 pathogenic Congenital amegakaryocytic thrombocytopenia 2020-09-16 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.