Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory of Diagnosis and Therapy of Lysosomal Disorders, |
RCV000677583 | SCV000803100 | 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 GnomAD (PM2) |
| Labcorp Genetics |
RCV000677583 | SCV003287604 | uncertain significance | Mucopolysaccharidosis type 6 | 2022-07-04 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 223 of the ARSB protein (p.Ile223Val). This variant is present in population databases (rs367650121, gnomAD 0.01%). This missense change has been observed in individual(s) with mucopolysaccharidosis type VI (PMID: 17458871). ClinVar contains an entry for this variant (Variation ID: 559803). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Revvity Omics, |
RCV000677583 | SCV003825031 | uncertain significance | Mucopolysaccharidosis type 6 | 2022-08-25 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000677583 | SCV003922649 | likely pathogenic | Mucopolysaccharidosis type 6 | 2023-03-18 | criteria provided, single submitter | clinical testing | Variant summary: ARSB c.667A>G (p.Ile223Val) results in a conservative amino acid change located in the Sulfatase, N-terminal domain (IPR000917) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 6e-05 in 251246 control chromosomes (gnomAD). This frequency is not significantly higher than estimated for a pathogenic variant in ARSB causing Mucopolysaccharidosis Type VI (Maroteaux-Lamy Syndrome) (6e-05 vs 0.0022), allowing no conclusion about variant significance. c.667A>G has been reported in the literature in at least one homozygous individual affected with Mucopolysaccharidosis Type VI (Maroteaux-Lamy Syndrome, Karageorgos_2007). These data indicate that the variant may be associated with disease. Fibroblasts from this homozygous patient had reduced ARSB protein expression and undetectable ARSB activity (Karageorgos_2007). Three ClinVar submitters have assessed the variant since 2014: two classified the variant as uncertain significance and one as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Baylor Genetics | RCV000677583 | SCV004208704 | likely pathogenic | Mucopolysaccharidosis type 6 | 2024-03-27 | criteria provided, single submitter | clinical testing |