ClinVar Miner

Submissions for variant NM_000046.5(ARSB):c.1334C>T (p.Pro445Leu) (rs1554069775)

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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 RCV000677475 SCV000802984 uncertain significance Mucopolysaccharidosis type 6 2018-01-01 criteria provided, single submitter curation Absent from GnomAD (PM2); Multiple lines of computational evidence support a deleterious effect on the gene product (PP3)
Invitae RCV000677475 SCV001374478 uncertain significance Mucopolysaccharidosis type 6 2019-09-11 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 445 of the ARSB protein (p.Pro445Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been observed as homozygous in an individual affected with mucopolysaccharidosis type VI but it co-occurs with another homozygous ARSB variant in cis (PMID: 24677745). ClinVar contains an entry for this variant (Variation ID: 559701). Experimental studies have shown that this missense change abrogates ARSB enzyme activity (PMID: 27826022). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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