ClinVar Miner

Submissions for variant NM_000046.5(ARSB):c.275C>A (p.Thr92Lys)

dbSNP: rs751010538
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Total submissions: 4
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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 RCV000677534 SCV000803045 uncertain significance Mucopolysaccharidosis type 6 2018-01-01 criteria provided, single submitter curation Absent from GnomAD (PM2); Reputable source identifies as pathogenic (PP5)
Invitae RCV000677534 SCV003525800 pathogenic Mucopolysaccharidosis type 6 2022-06-23 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Thr92 amino acid residue in ARSB. Other variant(s) that disrupt this residue have been observed in individuals with ARSB-related conditions (PMID: 8651289, 29202552), which suggests that this may be a clinically significant amino acid residue. 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: 559758). This missense change has been observed in individual(s) with mucopolysaccharidosis type VI (PMID: 17458871, 30982216). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with lysine, which is basic and polar, at codon 92 of the ARSB protein (p.Thr92Lys).
PreventionGenetics, part of Exact Sciences RCV003392515 SCV004110713 likely pathogenic ARSB-related condition 2023-09-30 criteria provided, single submitter clinical testing The ARSB c.275C>A variant is predicted to result in the amino acid substitution p.Thr92Lys. This variant was reported in the compound heterozygous and homozygous state in several unrelated individuals with mucopolysaccharidosis VI (Supp. Table 1 in Karageorgos et al 2007. PubMed ID: 17458871; Jafaryazdi R et al 2019. PubMed ID: 30982216). Other amino acid substitutions at this position (p.Thr92Met, p.Thr92Pro) have also been reported in patients with mucopolysaccharidosis VI (Litjens et al 1996. PubMed ID: 8651289; Abbasi et al 2017. PubMed ID: 29202552). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant is interpreted as likely pathogenic.
Baylor Genetics RCV000677534 SCV004209925 pathogenic Mucopolysaccharidosis type 6 2023-02-23 criteria provided, single submitter clinical testing

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