Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000795605 | SCV000935073 | pathogenic | Metachromatic leukodystrophy | 2023-10-13 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 288 of the ARSA protein (p.Thr288Pro). This variant is present in population databases (rs28940894, gnomAD 0.06%). This missense change has been observed in individual(s) with metachromatic leukodystrophy (PMID: 11061266, 12035837). This variant is also known as Thr286Pro. ClinVar contains an entry for this variant (Variation ID: 3090). 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. Experimental studies have shown that this missense change affects ARSA function (PMID: 12035837). For these reasons, this variant has been classified as Pathogenic. |
OMIM | RCV000003236 | SCV000023394 | pathogenic | Metachromatic leukodystrophy, adult type | 2000-10-10 | no assertion criteria provided | literature only | |
Natera, |
RCV000795605 | SCV002081655 | pathogenic | Metachromatic leukodystrophy | 2020-09-23 | no assertion criteria provided | clinical testing |