Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory of Diagnosis and Therapy of Lysosomal Disorders, |
RCV000677612 | SCV000803130 | uncertain significance | Mucopolysaccharidosis type 6 | 2018-01-01 | criteria provided, single submitter | curation | Absent from GnomAD (PM2); Change at an amino acid residue where a different change is pathogenic (PM5); Multiple lines of computational evidence support a deleterious effect on the gene product (PP3) |
| Labcorp Genetics |
RCV000677612 | SCV004293555 | likely pathogenic | Mucopolysaccharidosis type 6 | 2023-03-18 | 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. This variant disrupts the p.Arg315 amino acid residue in ARSB. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10036316, 17161971, 17458871, 26937411). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. ClinVar contains an entry for this variant (Variation ID: 559829). This missense change has been observed in individual(s) with mucopolysaccharidosis type VI (PMID: 26937411). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 315 of the ARSB protein (p.Arg315Pro). |