ClinVar Miner

Submissions for variant NM_005373.3(MPL):c.185C>T (p.Thr62Ile)

gnomAD frequency: 0.00001  dbSNP: rs201727975
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genome-Nilou Lab RCV001578625 SCV001805878 uncertain significance Congenital amegakaryocytic thrombocytopenia 2021-07-14 criteria provided, single submitter clinical testing
GeneDx RCV001751802 SCV001987076 uncertain significance not provided 2019-04-01 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001844301 SCV002103777 uncertain significance not specified 2022-02-24 criteria provided, single submitter clinical testing Variant summary: MPL c.185C>T (p.Thr62Ile) results in a non-conservative amino acid change located in the Growth hormone/erythropoietin receptor, ligand binding domain (IPR015152) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4.8e-05 in 251212 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in MPL causing Congenital Amegakaryocytic Thrombocytopenia (4.8e-05 vs 0.0024), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.185C>T in individuals affected with Congenital Amegakaryocytic Thrombocytopenia and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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