ClinVar Miner

Submissions for variant NM_000487.6(ARSA):c.1292A>C (p.Tyr431Ser)

gnomAD frequency: 0.00002  dbSNP: rs199476380
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001854228 SCV002261438 pathogenic Metachromatic leukodystrophy 2023-12-14 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with serine, which is neutral and polar, at codon 431 of the ARSA protein (p.Tyr431Ser). This variant is present in population databases (rs199476380, gnomAD 0.003%). This missense change has been observed in individual(s) with metachromatic leukodystrophy (PMID: 14517960; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as c.1286A>C (p.Tyr429Ser). ClinVar contains an entry for this variant (Variation ID: 68120). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ARSA protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
UniProtKB/Swiss-Prot RCV000058950 SCV000090471 not provided not provided no assertion provided not provided

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.