ClinVar Miner

Submissions for variant NM_005373.3(MPL):c.1178C>T (p.Thr393Ile)

gnomAD frequency: 0.00001  dbSNP: rs779132175
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000698792 SCV000827478 uncertain significance Congenital amegakaryocytic thrombocytopenia; Essential thrombocythemia 2023-11-01 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 393 of the MPL protein (p.Thr393Ile). This variant is present in population databases (rs779132175, gnomAD 0.006%). 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: 576320). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MPL protein function. 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.
Fulgent Genetics, Fulgent Genetics RCV002485709 SCV002775422 uncertain significance Congenital amegakaryocytic thrombocytopenia; Primary myelofibrosis; Thrombocythemia 2 2021-08-30 criteria provided, single submitter clinical testing
Natera, Inc. RCV001825373 SCV002086034 uncertain significance Congenital amegakaryocytic thrombocytopenia 2019-11-11 no assertion criteria provided clinical testing

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