ClinVar Miner

Submissions for variant NM_005373.3(MPL):c.1474_1477dup (p.Ser493fs)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001034960 SCV001198263 pathogenic Congenital amegakaryocytic thrombocytopenia; essential thrombocytemia 2019-02-20 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the MPL gene (p.Ser493Tyrfs*53). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 143 amino acids of the MPL protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MPL-related conditions. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the affected amino acid(s) is currently unknown. This variant disrupts the C-terminus of the MPL protein. Other variants that disrupt this region (p.Pro635Leu, p.Tyr542Leufs*3) have been observed in individuals with MPL-related conditions (PMID: 29384262,11071383, 18422784, 10971406). This suggests that this may be a clinically significant region of the protein. For these reasons, this variant has been classified as Pathogenic.

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