Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000078004 | SCV000109842 | uncertain significance | not provided | 2013-07-26 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV002514369 | SCV003525878 | 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.Trp312 amino acid residue in ARSB. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 14974081). 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: 92355). This variant has not been reported in the literature in individuals affected with ARSB-related conditions. This variant is present in population databases (rs398123124, gnomAD 0.002%). This sequence change replaces tryptophan, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 312 of the ARSB protein (p.Trp312Arg). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004586539 | SCV005075805 | uncertain significance | not specified | 2024-04-03 | criteria provided, single submitter | clinical testing | Variant summary: ARSB c.934T>C (p.Trp312Arg) results in a non-conservative amino acid change located in the Sulfatase, N-terminal domain (IPR000917) of 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 8e-06 in 251332 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.934T>C in individuals affected with Mucopolysaccharidosis Type VI (Maroteaux-Lamy Syndrome) and no experimental evidence demonstrating its impact on protein function have been reported. Additionally, one variant at the Trp312 residue has been reported in HGMD and ClinVar (p.Trp312Cys. LP/VUS in ClinVar), suggesting that this codon might be functionally important. ClinVar contains an entry for this variant (Variation ID: 92355). Based on the evidence outlined above, the variant was classified as uncertain significance. |