ClinVar Miner

Submissions for variant NM_005373.3(MPL):c.407C>G (p.Pro136Arg)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Dept. of Cytogenetics, ICMR- National Institute of Immunohaematology RCV003154848 SCV003843869 likely pathogenic Congenital amegakaryocytic thrombocytopenia criteria provided, single submitter clinical testing
Neuberg Centre For Genomic Medicine, NCGM RCV004763608 SCV005373598 likely pathogenic Congenital amegakaryocytic thrombocytopenia 1 2023-06-02 criteria provided, single submitter clinical testing The observed missense c.407C>G (p.Pro136Arg) variant in MPL gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. Another missense variant on the same residue [c.407C>T; p.Pro136Leu] in MPL gene has been reported previously to be disease causing in individuals affected with MPL-related disorders, suggesting that this residue might be of clinical significance (Germeshausen and Ballmaier, 2021). The p.Pro136Arg variant is present with allele frequency of 0.0004% in gnomAD Exomes. This variant has been submitted to the ClinVar database as Likely Pathogenic. The reference amino acid of p.Pro136Arg in MPL is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Pro at position 136 is changed to a Arg changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as a Variant of Uncertain Significance (VUS).
Fulgent Genetics, Fulgent Genetics RCV005029924 SCV005651167 likely pathogenic Primary myelofibrosis; Thrombocythemia 2; Congenital amegakaryocytic thrombocytopenia 1 2024-03-07 criteria provided, single submitter clinical testing

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