ClinVar Miner

Submissions for variant NM_000046.5(ARSB):c.1340G>T (p.Cys447Phe) (rs1465993279)

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Total submissions: 2
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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 RCV000677480 SCV000802989 uncertain significance Mucopolysaccharidosis type 6 2018-01-01 criteria provided, single submitter curation Absent from GnomAD (PM2)
Invitae RCV000677480 SCV000938808 pathogenic Mucopolysaccharidosis type 6 2020-07-09 criteria provided, single submitter clinical testing This sequence change replaces cysteine with phenylalanine at codon 447 of the ARSB protein (p.Cys447Phe). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with mucopolysaccharidosis type VI (PMID: 17458871, 17643332, 26909334). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 559706). This variant has been reported to affect ARSB protein function (PMID: 17458871). This variant disrupts the p.Cys447 amino acid residue in ARSB. Other variant that disrupt this residue have been observed in individuals with ARSB-related conditions (PMID: 17458871), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.

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