ClinVar Miner

Submissions for variant NM_005373.2(MPL):c.235_236del (p.Leu79fs) (rs587778514)

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Total submissions: 4
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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
Integrated Genetics/Laboratory Corporation of America 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 thrombocytemia 2019-10-14 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. This variant is present in population databases (rs587778514, ExAC 0.01%). This variant has been observed in several individuals affected with congenital amegakaryocytic thrombocytopenia (PMID: 11133753, 17666371). This variant is also known as del235/236 in the literature. ClinVar contains an entry for this variant (Variation ID: 134822). Loss-of-function variants in MPL are known to be pathogenic (PMID: 8073287, 11133753). 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

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