ClinVar Miner

Submissions for variant NM_001171.5(ABCC6):c.1171A>G (p.Arg391Gly) (rs72653762)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Praxis fuer Humangenetik Tuebingen RCV000256117 SCV000780531 uncertain significance not provided 2018-09-30 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000256117 SCV000700696 uncertain significance not provided 2017-05-08 criteria provided, single submitter clinical testing
GeneDx RCV000256117 SCV000321360 pathogenic not provided 2018-11-12 criteria provided, single submitter clinical testing The R391G variant in the ABCC6 gene has been previously reported in association with pseudoxanthoma elasticum (PXE) (Chassaing et al., 2004; Pfendner et al., 2007; Pfendner et al., 2008) and generalized arterial calcification of infancy (GACI) (Nitschke et al., 2012). The variant has also been observed at GeneDx in the compound heterozygous state with another pathogenic variant in multiple affected individuals. The variant is observed in 993/126248 (0.7865%) alleles from individuals of European background in large population cohorts, likely reflecting the presence of pseudogene 1 (where R391G is always found) contamination in the sample (Lek et al., 2016). R391G 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. In summary, we consider this variant to be pathogenic.
Genomic Research Center,Shahid Beheshti University of Medical Sciences RCV000499064 SCV000845610 uncertain significance Pseudoxanthoma elasticum 2018-08-07 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000455861 SCV000538215 uncertain significance not specified 2016-03-28 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Reported in an individual with cutanous Pseudoxanthoma Elasticum who also had a multi exon deletion in ABCC6 (Chassing 2004). Also reported in two probands and in one affected twin sibling with generalized arterial calcification of infancy (Nitschke 2012), one of whom also had a frameshift variant. This was the only variant identified in the twins. MAF 0.8% with 3 homozygotes in ExAC.
PXE International RCV000499064 SCV000588952 pathogenic Pseudoxanthoma elasticum no assertion criteria provided research

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