ClinVar Miner

Submissions for variant NM_005373.3(MPL):c.1337G>A (p.Gly446Glu)

gnomAD frequency: 0.00001  dbSNP: rs561724539
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000379998 SCV000357780 uncertain significance Thrombocythemia 1 2016-06-14 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000266369 SCV000357781 uncertain significance Congenital amegakaryocytic thrombocytopenia 2016-06-14 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002520491 SCV002962203 uncertain significance Congenital amegakaryocytic thrombocytopenia; Essential thrombocythemia 2021-08-30 criteria provided, single submitter clinical testing This sequence change replaces glycine with glutamic acid at codon 446 of the MPL protein (p.Gly446Glu). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and glutamic acid. This variant is present in population databases (rs561724539, ExAC 0.02%). This variant has not been reported in the literature in individuals affected with MPL-related conditions. ClinVar contains an entry for this variant (Variation ID: 297406). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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