ClinVar Miner

Submissions for variant NM_005373.3(MPL):c.1774C>T (p.Arg592Ter)

gnomAD frequency: 0.00001  dbSNP: rs755447085
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
Illumina Laboratory Services, Illumina RCV000778242 SCV000914410 uncertain significance MPL-related disorder 2018-10-23 criteria provided, single submitter clinical testing The MPL c.1774C>T (p.Arg592Ter) variant is a missense variant. A literature search was performed for the gene and cDNA change. No publications were found based on this search. Control data are unavailable for this variant, which is reported at a frequency of 0.000162 in the South Asian population of the Genome Aggregation Database. This variant occurs in the last exon and may escape nonsense-mediated decay. Based on the limited evidence, the p.Arg592Ter variant is classified as a variant of uncertain significance but suspicious for pathogenicity for MPL-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV002536728 SCV003247682 pathogenic Congenital amegakaryocytic thrombocytopenia; Essential thrombocythemia 2023-11-09 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg592*) in the MPL gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 44 amino acid(s) of the MPL protein. This variant is present in population databases (rs755447085, gnomAD 0.02%). This premature translational stop signal has been observed in individual(s) with clinical features of MPL-related conditions (PMID: 35776903). ClinVar contains an entry for this variant (Variation ID: 631607). This variant disrupts a region of the MPL protein in which other variant(s) (p.Pro635Leu) have been determined to be pathogenic (PMID: 10971406, 11071383, 18422784). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

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.