ClinVar Miner

Submissions for variant NM_000443.3(ABCB4):c.2800G>A (p.Ala934Thr) (rs61730509)

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
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000322710 SCV000331495 benign not specified 2015-08-24 criteria provided, single submitter clinical testing
GeneDx RCV000413855 SCV000491318 likely pathogenic not provided 2018-04-27 criteria provided, single submitter clinical testing The A934T variant has been reported previously as homozygous in one individual with low phospholipid-associated cholelithiasis (LPAC) syndrome; heterozygous parents were asymptomatic (Rosmorduc et al., 2003). The A934T variant was also reported as heterozygous in an individual with cholestatic liver disease; a second variant in the ABCB4 gene was not identified (Gordo-Gilart et al., 2016). In vitro functional studies showed the A934T allele lead to reduced MDR3 protein levels (65%) and MDR3 activity (50%), which resulted in trapping of the ABCB4 protein in the endoplasmic reticulum (Gordo-Gilart et al., 2016). The NHLBI Exome Sequencing Project and the 1000 Genomes Project Consortium reports A934T was observed in 1.2-2.8% of alleles from individuals of African background. The A934T variant is a non-conservative amino acid substitution, which occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.

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.