ClinVar Miner

Submissions for variant NM_000487.6(ARSA):c.746T>C (p.Phe249Ser)

gnomAD frequency: 0.00001  dbSNP: rs199476384
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
Invitae RCV000524971 SCV000627145 pathogenic Metachromatic leukodystrophy 2023-09-03 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 249 of the ARSA protein (p.Phe249Ser). This variant is present in population databases (rs199476384, gnomAD 0.003%). This missense change has been observed in individual(s) with metachromatic leukodystrophy (PMID: 14680985, 23701968, 24001781, 25965562, 26553228; 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 p.Phe247Ser. ClinVar contains an entry for this variant (Variation ID: 68149). 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. For these reasons, this variant has been classified as Pathogenic.
UniProtKB/Swiss-Prot RCV000058980 SCV000090501 not provided not provided no assertion provided not provided
Counsyl RCV000524971 SCV000789820 likely pathogenic Metachromatic leukodystrophy 2017-10-10 no assertion criteria provided clinical testing
Natera, Inc. RCV000524971 SCV002081662 pathogenic Metachromatic leukodystrophy 2020-09-03 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.