ClinVar Miner

Submissions for variant NM_000046.5(ARSB):c.304C>A (p.Arg102Ser)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003495428 SCV004248534 likely pathogenic Mucopolysaccharidosis type 6 2023-11-11 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 102 of the ARSB protein (p.Arg102Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ARSB-related conditions. 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%. This variant disrupts the p.Arg102 amino acid residue in ARSB. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 17161971, 17458871). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004701083 SCV005205282 uncertain significance not specified 2024-06-05 criteria provided, single submitter clinical testing Variant summary: ARSB c.304C>A (p.Arg102Ser) results in a non-conservative amino acid change located in the Sulfatase, N-terminal (IPR000917) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 104750 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.304C>A in individuals affected with Mucopolysaccharidosis Type VI (Maroteaux-Lamy Syndrome) and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 2694709). Based on the evidence outlined above, the variant was classified as uncertain significance.

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