ClinVar Miner

Submissions for variant NM_001171.5(ABCC6):c.3490C>T (p.Arg1164Ter) (rs72653744)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000255402 SCV000321367 pathogenic not provided 2018-12-20 criteria provided, single submitter clinical testing The R1164X pathogenic variant in the ABCC6 gene has been reported previously in association with pseudoxanthoma elasticum, as a prevalent pathogenic variant in European and American patient populations (Struk et al., 2000; Pfendner et al., 2007). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R1164X variant was not observed at any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret R1164X as a pathogenic variant.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000006950 SCV000271307 pathogenic Pseudoxanthoma elasticum 2015-03-11 criteria provided, single submitter clinical testing The p.Arg1164X variant in ABCC6 has been previously reported in the homozygous s tate in one family with Pseudoxanthoma Elasticum (PXE; Struk 2000) and in 2 hete rozygous individuals with PXE in which another variant was not identified (Melon i 2001, Chassaing 2004). This variant has also been identified in 0.05% (4/8652 ) East Asian chromosomes by the Exome Aggregation Consortium (http://exac.broadi nstitute.org/; dbSNP rs72653744). Although this variant has been seen in the gen eral population, its frequency is low enough to be consistent with a recessive c arrier frequency. This nonsense variant leads to a premature termination codon a t position 1164, which is predicted to lead to a truncated or absent protein. Co mplete loss of ABCC6 function is an established disease mechanism for PXE. In su mmary, this variant meets our criteria to be classified as pathogenic for PXE in an autosomal recessive manner (www.partners.org/personalizedmedicine/lmm).
OMIM RCV000006950 SCV000027146 pathogenic Pseudoxanthoma elasticum 2001-03-01 no assertion criteria provided literature only
PXE International RCV000006950 SCV000589062 pathogenic Pseudoxanthoma elasticum no assertion criteria provided research

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