ClinVar Miner

Submissions for variant NM_000046.5(ARSB):c.323G>T (p.Gly108Val)

dbSNP: rs768802200
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Baylor Genetics RCV000677546 SCV004208715 likely pathogenic Mucopolysaccharidosis type 6 2023-10-27 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000677546 SCV004293560 pathogenic Mucopolysaccharidosis type 6 2023-05-26 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. 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: 559769). This missense change has been observed in individual(s) with mucopolysaccharidosis type VI (PMID: 17161971, 30809705). This variant is present in population databases (rs768802200, gnomAD 0.003%). This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 108 of the ARSB protein (p.Gly108Val).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000677546 SCV005185235 pathogenic Mucopolysaccharidosis type 6 2024-05-20 criteria provided, single submitter clinical testing Variant summary: ARSB c.323G>T (p.Gly108Val) 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 4e-06 in 251330 control chromosomes. c.323G>T has been reported in the literature in multiple individuals affected with Mucopolysaccharidosis Type VI (Maroteaux-Lamy Syndrome) in the homozygous and compound heterozygous state (e.g. Karageorgos_2007, Zanetti_2019, Baheer Abdul Wahhab_2023). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 37811045, 17161971, 17458871, 30809705). ClinVar contains an entry for this variant (Variation ID: 559769). Based on the evidence outlined above, the variant was classified as pathogenic.
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova RCV000677546 SCV000803059 uncertain significance Mucopolysaccharidosis type 6 2018-01-01 flagged submission curation Very low frequency in ExAC (PM2)

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