ClinVar Miner

Submissions for variant NM_001171.5(ABCC6):c.3940C>T (p.Arg1314Trp) (rs63750759)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000254915 SCV000321369 pathogenic not provided 2019-01-03 criteria provided, single submitter clinical testing The R1314W variant in the ABCC6 gene has been reported previously in association with pseudoxanthoma elasticum (Le Saux et al., 2000; Ramsay et al., 2009; Arányi et al., 2013) and also in association with generalized arterial calcification of infancy (Nitschke et al., 2012; Li et al., 2014). Functional and expression studies in mouse models indicate that R1314W results in abnormal protein trafficking and inappropriate intracellular accumulation (Le Saux et al., 2011). The variant is observed in 47/18748 (0.25%) alleles from individuals of African background in large population cohorts (Lek et al., 2016). The variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs within the second ABC transporter domain at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. In summary, we interpret R1314W as a pathogenic variant.
OMIM RCV000006942 SCV000027138 pathogenic Pseudoxanthoma elasticum 2012-01-13 no assertion criteria provided literature only
OMIM RCV000023273 SCV000044564 pathogenic Generalized arterial calcification of infancy 2 2012-01-13 no assertion criteria provided literature only
PXE International RCV000006942 SCV000589091 pathogenic Pseudoxanthoma elasticum no assertion criteria provided 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.