ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.813del (p.Arg271fs)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001376889 SCV001574075 likely pathogenic Familial platelet disorder with associated myeloid malignancy 2020-07-07 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the RUNX1 gene (p.Arg271Serfs*40). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 210 amino acids of the RUNX1 protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with RUNX1-related conditions. This variant disrupts the transcriptional activation domain (amino acid residues 318-398), DNA-binding inhibitory domain (residues 398-438), and VWRPY domain (residues 476-480) of the RUNX1 protein (PMID: 22689681, 23753029, 15749889, 14504086). While functional studies have not been performed to directly test the effect of this variant on RUNX1 protein function, this suggests that disruption of this region of the protein is causative of disease. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely 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.