Submissions for variant NM_000046.5(ARSB):c.288C>G (p.Ser96Arg)

dbSNP: rs1554032095

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Medical Molecular Genetics Department, National Research Center	RCV000656131	SCV000609485	pathogenic	Mucopolysaccharidosis type 6	2015-12-01	criteria provided, single submitter	research
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova	RCV000656131	SCV000803050	uncertain significance	Mucopolysaccharidosis type 6	2018-01-01	criteria provided, single submitter	curation	Absent from GnomAD (PM2)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001584227	SCV001821505	uncertain significance	not specified	2021-08-10	criteria provided, single submitter	clinical testing	Variant summary: ARSB c.288C>G (p.Ser96Arg) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 142908 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.288C>G has been reported in the literature in one individual affected with Mucopolysaccharidosis Type VI (Maroteaux-Lamy Syndrome). This report does not provide unequivocal conclusions about association of the variant with Mucopolysaccharidosis Type VI (Maroteaux-Lamy Syndrome). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as pathogenic, and one laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.