Total submissions: 2
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. |
Uni |
RCV000058950 | SCV000090471 | not provided | not provided | no assertion provided | not provided |