ClinVar Miner

Submissions for variant NM_000487.6(ARSA):c.1046del (p.Pro349fs) (rs1603444908)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000818754 SCV000959384 pathogenic Metachromatic leukodystrophy 2018-11-19 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the ARSA gene (p.Pro349Hisfs*74). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 161 amino acids of the ARSA protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be homozygous in an individual affected with metachromatic leukodystrophy (PMID: 10220151). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the affected amino acid(s) is currently unknown. This variant disrupts the p.Glu384 amino acid residue in ARSA. Other variant(s) that disrupt this residue have been observed in affected individuals (PMID: 26462614, 7906588, 15375602, 20339381, 19021637), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.

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.