ClinVar Miner

Submissions for variant NM_020774.3(MIB1):c.1588C>T (p.Arg530Ter) (rs201850378)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000485600 SCV000568835 uncertain significance not provided 2017-12-06 criteria provided, single submitter clinical testing The R530X variant of uncertain significance in the MIB1 gene has been previously reported in one Southern European individual diagnosed with LVNC and was shown to segregate with disease in five additional affected relatives (Luxán et al., 2013). Using blood samples from affected relatives harboring R530X, Luxán et al. (2013) demonstrated that mutant mRNA expression is almost completely abolished and truncated MIB1 protein is not detectable, suggesting that R530X causes loss of protein expression through nonsense-mediated mRNA decay. Blood samples from these affected carriers also showed reduced NOTCH1 activity and target-gene expression (Luxán et al., 2013). In addition, the R530X variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). Nevertheless, only four other variants in the MIB1 gene have been reported in HGMD in association with MIB1-related disorders, and no other truncating variants in the MIB1 gene have been reported in association with cardiomyopathy (Stenson et al., 2014). Thus, the mechanism of disease for variants in the MIB1 gene remains to be definitely established. Identification of the R530X variant in additional affected individuals, larger segregation studies, and further functional evidence are necessary to further clarify the role of this variant in disease.Therefore, additional evidence is needed to determine whether this variant is pathogenic or benign.
Genome Diagnostics Laboratory,University Medical Center Utrecht RCV000033170 SCV000743478 likely pathogenic Left ventricular noncompaction 7 2016-11-17 criteria provided, single submitter clinical testing
OMIM RCV000033170 SCV000056952 pathogenic Left ventricular noncompaction 7 2013-02-01 no assertion criteria provided literature only

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.