Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, |
RCV000677600 | SCV000803117 | 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); Absent from GnomAD (PM2) |
Invitae | RCV000677600 | SCV004293558 | likely pathogenic | Mucopolysaccharidosis type 6 | 2023-10-28 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with asparagine, which is neutral and polar, at codon 296 of the ARSB protein (p.Ile296Asn). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with mucopolysaccharidosis type VI (PMID: 17458871). ClinVar contains an entry for this variant (Variation ID: 559817). 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 ARSB protein function with a positive predictive value of 95%. 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. |