Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Medical Molecular Genetics Department, |
RCV000656128 | SCV000609482 | pathogenic | Mucopolysaccharidosis type 6 | 2015-12-01 | criteria provided, single submitter | research | |
SIB Swiss Institute of Bioinformatics | RCV000656128 | SCV000787487 | likely pathogenic | Mucopolysaccharidosis type 6 | 2018-04-16 | criteria provided, single submitter | curation | This variant is interpreted as a Likely Pathogenic, for Mucopolysaccharidosis type VI, Autosomal Recessive inheritance. The following ACMG Tag(s) were applied: PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PS3 => Well-established functional studies show a deleterious effect (PMID:18406185). PM3 => For recessive disorders, detected in trans with a pathogenic variant (PMID:19259130). |
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, |
RCV000656128 | SCV000803033 | 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 frequence in ExAC (PM2) |
Invitae | RCV000656128 | SCV001579936 | pathogenic | Mucopolysaccharidosis type 6 | 2023-10-23 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 82 of the ARSB protein (p.Leu82Arg). This variant is present in population databases (no rsID available, gnomAD 0.001%). This missense change has been observed in individual(s) with mucopolysaccharidosis type VI (PMID: 17643332, 19259130). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 445290). 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. Experimental studies have shown that this missense change affects ARSB function (PMID: 18406185). For these reasons, this variant has been classified as Pathogenic. |
Baylor Genetics | RCV000656128 | SCV004209903 | pathogenic | Mucopolysaccharidosis type 6 | 2023-03-08 | criteria provided, single submitter | clinical testing |