ClinVar Miner

Submissions for variant NM_001171.5(ABCC6):c.4016G>A (p.Arg1339His) (rs63750622)

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
GeneDx RCV000255253 SCV000321370 likely pathogenic not provided 2016-03-04 criteria provided, single submitter clinical testing The R1339H variant in the ABCC6 gene has been reported at least seven times previously in association with PXE (Miksch et al., 2005, Pfendner et al. 2007, Vanakker et al., 2008). The R1339H variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R1339H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species In silico analysis predicts this variant is probably damaging to the protein structure/function as it occurs in the highly conserved second ATP binding domain required for proper gene function and in which numerous pathogenic variants are clustered. Missense variants at the same residue (R1339C, R1339L) and in nearby residues (L1335P, L1335Q, I1342T) have been reported in the Human Gene Mutation Database in association with PXE (Stenson et al., 2014), supporting the functional importance of this region of the protein. According to the ACMG Guidelines this variant is classified as likely pathogenic; however, the unlikely possibility that it is benign cannot be excluded.
PXE International RCV000499080 SCV000589101 pathogenic Pseudoxanthoma elasticum criteria provided, single submitter research

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.