ClinVar Miner

Submissions for variant NM_005373.3(MPL):c.1612G>C (p.Val538Leu)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003778159 SCV004570826 uncertain significance Congenital amegakaryocytic thrombocytopenia; Essential thrombocythemia 2024-07-25 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 538 of the MPL protein (p.Val538Leu). This variant is present in population databases (rs374829965, gnomAD 0.005%). This missense change has been observed in individual(s) with congenital amegakaryocytic thrombocytopenia (PMID: 32703794). ClinVar contains an entry for this variant (Variation ID: 2627079). 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) performed at Invitae indicates that this missense variant is not expected to disrupt MPL protein function with a negative predictive value of 95%. 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.
Zotz-Klimas Genetics Lab, MVZ Zotz Klimas RCV003388277 SCV004099457 uncertain significance Thrombocythemia 2 2023-10-30 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.