Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Neurometabolisches Labor, |
RCV000496179 | SCV000586689 | pathogenic | Metachromatic leukodystrophy | 2017-05-01 | criteria provided, single submitter | research | |
Counsyl | RCV000496179 | SCV000795877 | uncertain significance | Metachromatic leukodystrophy | 2017-11-21 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000496179 | SCV002306085 | likely pathogenic | Metachromatic leukodystrophy | 2023-01-12 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies have shown that this missense change affects ARSA function (PMID: 28762252). 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: 431088). This missense change has been observed in individual(s) with metachromatic leukodystrophy (PMID: 28762252). This variant is present in population databases (rs527640350, gnomAD 0.05%). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 225 of the ARSA protein (p.Tyr225Cys). |