Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001237276 | SCV001410030 | pathogenic | Metachromatic leukodystrophy | 2022-11-08 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Cys302 amino acid residue in ARSA. Other variant(s) that disrupt this residue have been observed in individuals with ARSA-related conditions (PMID: 33385934), which suggests that this may be a clinically significant amino acid residue. 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. ClinVar contains an entry for this variant (Variation ID: 963270). This missense change has been observed in individual(s) with clinical features of metachromatic leukodystrophy (PMID: 32632536; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 302 of the ARSA protein (p.Cys302Tyr). |
Amsterdam Leukodystrophy Center, |
RCV001237276 | SCV001424852 | pathogenic | Metachromatic leukodystrophy | 2020-06-24 | criteria provided, single submitter | clinical testing | Homozygous - novel (late-infantile MLD) |