Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, |
RCV000677472 | SCV000802980 | likely pathogenic | Mucopolysaccharidosis type 6 | 2018-01-01 | criteria provided, single submitter | curation | In vitro functional studies supportive of a damaging effect on the gene product (low to no ARSB activity in homozygotes; PS3); Very low frequency in ExAC (PM2) |
Labcorp Genetics |
RCV000677472 | SCV001575981 | likely pathogenic | Mucopolysaccharidosis type 6 | 2022-08-06 | criteria provided, single submitter | clinical testing | This missense change has been observed in individual(s) with mucopolysaccharidosis type VI (PMID: 17161971, 17458871). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 430 of the ARSB protein (p.His430Arg). ClinVar contains an entry for this variant (Variation ID: 559698). 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 ARSB function (PMID: 17161971). 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 not expected to disrupt ARSB protein function. |