ClinVar Miner

Submissions for variant NM_000046.5(ARSB):c.1350G>C (p.Trp450Cys) (rs555785323)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory of Diagnosis and Therapy of Lysosomal Disorders,University of Padova RCV000677482 SCV000802991 likely pathogenic Mucopolysaccharidosis type 6 2018-01-01 criteria provided, single submitter curation In vitro functional studies supportive of a damaging effect on the gene product (low to no ARSB activity in homozygotes; PS3); Very low frequency in ExAC (PM2); Multiple lines of computational evidence support a deleterious effect on the gene product (PP3)
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000732121 SCV000860029 likely pathogenic not provided 2018-03-23 criteria provided, single submitter clinical testing
Invitae RCV000677482 SCV001583437 pathogenic Mucopolysaccharidosis type 6 2020-10-18 criteria provided, single submitter clinical testing This sequence change replaces tryptophan with cysteine at codon 450 of the ARSB protein (p.Trp450Cys). The tryptophan residue is highly conserved and there is a large physicochemical difference between tryptophan and cysteine. This variant is present in population databases (rs555785323, ExAC 0.01%). This variant has been observed in individual(s) with mucopolysaccharidosis type VI (PMID: 27826022). ClinVar contains an entry for this variant (Variation ID: 559708). 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. Experimental studies have shown that this variant affects ARSB protein function (PMID: 27826022). For these reasons, this variant has been classified as Pathogenic.

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