Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory of Diagnosis and Therapy of Lysosomal Disorders, |
RCV000677542 | SCV000803055 | uncertain significance | Mucopolysaccharidosis type 6 | 2018-01-01 | criteria provided, single submitter | curation | Absent from GnomAD (PM2) |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001779055 | SCV002015094 | uncertain significance | not specified | 2021-10-28 | criteria provided, single submitter | clinical testing | Variant summary: ARSB c.305G>A (p.Arg102His) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.9e-05 in 104750 control chromosomes. c.305G>A has been reported in the literature in individuals affected with Mucopolysaccharidosis Type VI (Maroteaux-Lamy Syndrome, Karageorgos_MGM_2007, Karageorgos_HumMut_2007). These data do not allow any conclusion about variant significance. Co-occurrence with a pathogenic variant has been reported (ARSB del exon 5), providing supporting evidence for a benign role. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in 10%-<30% of normal activity (Karageorgos_MGM_2007). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |
| Labcorp Genetics |
RCV000677542 | SCV002261481 | likely pathogenic | Mucopolysaccharidosis type 6 | 2024-01-11 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 102 of the ARSB protein (p.Arg102His). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with mucopolysaccharidosis type VI (PMID: 17161971, 17458871). ClinVar contains an entry for this variant (Variation ID: 559766). 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%. Studies have shown that this missense change alters ARSB gene expression (PMID: 17161971). 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. |
| Baylor Genetics | RCV000677542 | SCV004209225 | likely pathogenic | Mucopolysaccharidosis type 6 | 2024-01-25 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV000677542 | SCV005673126 | likely pathogenic | Mucopolysaccharidosis type 6 | 2024-05-15 | criteria provided, single submitter | clinical testing |