ClinVar Miner

Submissions for variant NM_001171.5(ABCC6):c.3421C>T (p.Arg1141Ter) (rs72653706)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 13
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000254838 SCV000321366 pathogenic not provided 2019-01-03 criteria provided, single submitter clinical testing The R1141X variant is one of the most common pathogenic variants in the ABCC6 gene and has been reported previously either in the homozygous state or in combination with another ABCC6 variant in multiple unrelated individuals with pseudoxanthoma elasticum or generalized arterial calcification of infancy (Ringpfeil et al., 2000; Hu et al., 2003; Miksch et al., 2005; Nitschke et al., 2012; Akoglu et al., 2014). It has been suggested that heterozygosity for this variant may increase the risk of coronary artery disease, but this association has not been confirmed in the largest study (Trip et al., 2002; Hornstrup et al., 2011). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Expression studies of the R1141X variant in leukocytes and cultured fibroblasts from affected individuals homozygous for R1141X demonstrated that this variant leads to mRNA instability and absence of the protein in immunohistochemistry studies (Hu et al., 2003). The R1141X variant is observed in 20/6,614 (0.3%) alleles from individuals of European (Finnish) background and 140/66,508 (0.2%) from individuals of European (non-Finnish) background in the ExAC dataset (Lek et al., 2015). We interpret R1141X as a pathogenic variant.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000254838 SCV000331362 pathogenic not provided 2016-03-02 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000415101 SCV000492948 pathogenic Cutis laxa; Papule 2014-10-24 criteria provided, single submitter clinical testing
Genetic Services Laboratory,University of Chicago RCV000006937 SCV000592960 pathogenic Pseudoxanthoma elasticum 2016-08-17 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000762959 SCV000893397 pathogenic Pseudoxanthoma elasticum; Pseudoxanthoma elasticum, forme fruste; Generalized arterial calcification of infancy 2 2018-10-31 criteria provided, single submitter clinical testing
Blueprint Genetics RCV000254838 SCV000927190 pathogenic not provided 2017-03-06 criteria provided, single submitter clinical testing
Victorian Clinical Genetics Services,Murdoch Childrens Research Institute RCV000023272 SCV001244971 pathogenic Generalized arterial calcification of infancy 2 2018-04-16 criteria provided, single submitter clinical testing A heterozygous nonsense variant, NM_001171.5(ABCC6):c.3421C>T, has been identified in exon 24 of 31 of the ABCC6 gene. The variant is predicted to result in a premature stop codon at position 1141 of the protein (NP_001162.4(ABCC6):p.(Arg1141*)). This variant has been shown to result in loss of protein function (including the ABC transporter transmembrane region and ABC transporter domain) through nonsense-mediated decay (Le Saux O., et al. (2001), which is a reported mechanism of pathogenicity for this gene. The variant is present in the gnomAD database at a frequency of 0.136% (0 homozygotes). The variant has been previously described as a common pathogenic variant and segregates with disease (ClinVar, Le Saux O., et al. (2000)). Additionally, no detectable ABCC6 mRNA was obtained from skin fibroblasts derived from a patient homozygous for this variant (Le Saux O., et al. (2001)). Multiple upstream and downstream truncating variants have been previously reported as pathogenic (ClinVar). Analysis of parental samples indicated this variant was paternally inherited, but was not identified in the maternal sample. Based on the information available at the time of curation, this variant has been classified as PATHOGENIC.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000254838 SCV001245824 pathogenic not provided 2017-06-01 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV001198516 SCV001369480 pathogenic Ichthyosis (disease) 2016-01-01 criteria provided, single submitter clinical testing This variant was classified as: Uncertain significance. This variant was detected in heterozygous state.
OMIM RCV000006937 SCV000027133 pathogenic Pseudoxanthoma elasticum 2012-01-13 no assertion criteria provided literature only
OMIM RCV000023272 SCV000044563 pathogenic Generalized arterial calcification of infancy 2 2012-01-13 no assertion criteria provided literature only
PXE International RCV000006937 SCV000589060 pathogenic Pseudoxanthoma elasticum no assertion criteria provided research
Sharon lab,Hadassah-Hebrew University Medical Center RCV000006937 SCV001160875 pathogenic Pseudoxanthoma elasticum 2019-06-23 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.