ClinVar Miner

Submissions for variant NM_000487.6(ARSA):c.474C>A (p.Cys158Ter) (rs768028181)

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 RCV000254939 SCV000322395 pathogenic not provided 2016-04-14 criteria provided, single submitter clinical testing The C158X pathogenic variant in the ARSA gene has been reported previously in both the compound heterozygous and homozygous state in association with metachromatic leukodystrophy (Luzi et al., 2013). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The C158X variant was not observed in approximately 6400 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 C158X as a pathogenic variant.
Invitae RCV000984244 SCV001224437 pathogenic Metachromatic leukodystrophy 2020-03-09 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Cys158*) in the ARSA gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs768028181, ExAC 0.03%). This variant has been observed in individuals affected with metachromatic leukodystrophy (PMID: 24001781). This variant is also known as 468C>A, p.C156X in the literature. ClinVar contains an entry for this variant (Variation ID: 265461). Loss-of-function variants in ARSA are known to be pathogenic (PMID: 8962139, 10477432). For these reasons, this variant has been classified as Pathogenic.
Counsyl RCV000984244 SCV001132337 likely pathogenic Metachromatic leukodystrophy 2015-07-17 no assertion criteria provided clinical testing
Natera, Inc. RCV000984244 SCV001462390 pathogenic Metachromatic leukodystrophy 2020-09-16 no assertion criteria provided clinical testing

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.