ClinVar Miner

Submissions for variant NM_000046.5(ARSB):c.936G>T (p.Trp312Cys)

dbSNP: rs759384989
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
SIB Swiss Institute of Bioinformatics RCV000664057 SCV000787484 likely pathogenic Mucopolysaccharidosis type 6 2018-04-16 criteria provided, single submitter curation This variant is interpreted as a Likely Pathogenic, for Mucopolysaccharidosis type VI, Autosomal Recessive inheritance. The following ACMG Tag(s) were applied: PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PS3 => Well-established functional studies show a deleterious effect (PMID:14974081).
Molecular Diagnostics Laboratory, M Health Fairview: University of Minnesota RCV000664057 SCV000891179 likely pathogenic Mucopolysaccharidosis type 6 2018-10-03 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000664057 SCV002275042 likely pathogenic Mucopolysaccharidosis type 6 2022-09-28 criteria provided, single submitter clinical testing This missense change has been observed in individual(s) with mucopolysaccharidosis type VI (PMID: 14974081). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tryptophan, which is neutral and slightly polar, with cysteine, which is neutral and slightly polar, at codon 312 of the ARSB protein (p.Trp312Cys). ClinVar contains an entry for this variant (Variation ID: 549491). 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. Experimental studies have shown that this missense change affects ARSB function (PMID: 14974081). 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.
3billion RCV000664057 SCV003841486 likely pathogenic Mucopolysaccharidosis type 6 2023-02-23 criteria provided, single submitter clinical testing The variant is not observed in the gnomAD v2.1.1 dataset. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.97; 3Cnet: 0.99). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000549491). A different missense change at the same codon (p.Trp312Arg) has been reported to be associated with ARSB-related disorder (PMID: 17458871). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline.
Baylor Genetics RCV000664057 SCV004209914 likely pathogenic Mucopolysaccharidosis type 6 2023-03-06 criteria provided, single submitter clinical testing

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