ClinVar Miner

Submissions for variant NM_000046.5(ARSB):c.765T>A (p.Tyr255Ter)

dbSNP: rs1554086414
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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 RCV000677595 SCV000803112 likely pathogenic Mucopolysaccharidosis type 6 2018-01-01 criteria provided, single submitter curation Nonsense variant (PVS1); Absent from GnomAD (PM2)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000677595 SCV001363605 pathogenic Mucopolysaccharidosis type 6 2019-10-17 criteria provided, single submitter clinical testing Variant summary: ARSB c.765T>A (p.Tyr255X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 251380 control chromosomes (gnomAD). c.765T>A has been reported in the literature in individuals affected with Mucopolysaccharidosis Type VI (Maroteaux-Lamy Syndrome)(But_2011, Tomanin_2018, Lam_2004). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. A ClinVar submission (evaluation after 2014) cite the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV000677595 SCV002137548 pathogenic Mucopolysaccharidosis type 6 2021-10-05 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 559812). This premature translational stop signal has been observed in individual(s) with mucopolysaccharidosis type VI (PMID: 15603718). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Tyr255*) in the ARSB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ARSB are known to be pathogenic (PMID: 17458871, 22133300).

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