ClinVar Miner

Submissions for variant NM_000046.5(ARSB):c.1507C>T (p.Gln503Ter) (rs771113472)

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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 RCV000677494 SCV000803004 likely pathogenic Mucopolysaccharidosis type 6 2018-01-01 criteria provided, single submitter curation Nonsense variant (PVS1); Very low frequency in ExAC (PM2)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000677494 SCV001572523 likely pathogenic Mucopolysaccharidosis type 6 2021-04-14 criteria provided, single submitter clinical testing Variant summary: ARSB c.1507C>T (p.Gln503X) results in a premature termination codon in the last exon, which is not expected to result in nonsense mediated decay (NMD), but predicted to cause a truncation of the encoded protein, removing 31 amino acids from the encoded protein. Truncations downstream of this position have been reported in affected individuals (HGMD). The variant allele was found at a frequency of 4e-06 in 251464 control chromosomes (gnomAD). The variant, c.1507C>T, has been reported in the literature in at least one apparently homozygous individual affected with Mucopolysaccharidosis Type VI of intermediate severity (Maroteaux-Lamy Syndrome) (Villani_1999). At least one publication reported greatly decreased enzyme activity, together with high levels of ARSB mRNA in patient derived fibroblast, indicating the lack of NMD (Bartolomeo_2012). One submitter has provided clinical-significance assessments for this variant in ClinVar after 2014 (without evidence for independent evaluation), and classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.

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