Submissions for variant NM_000046.5(ARSB):c.1079T>C (p.Leu360Pro)

dbSNP: rs1554079284

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova	RCV000677446	SCV000802949	likely pathogenic	Mucopolysaccharidosis type 6	2018-01-01	criteria provided, single submitter	curation	In vitro functional studies supportive of a damaging effect on the gene product (low to no ARSB activity in homozygotes; PS3); Absent from GnomAD (PM2); Multiple lines of computational evidence support a deleterious effect on the gene product (PP3)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000677446	SCV005205385	pathogenic	Mucopolysaccharidosis type 6	2024-06-03	criteria provided, single submitter	clinical testing	Variant summary: ARSB c.1079T>C (p.Leu360Pro) results in a non-conservative amino acid change located in the sulfatase, N-terminal domain (IPR000917) of 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 251248 control chromosomes (gnomAD). c.1079T>C has been reported in the literature in individuals affected with mild to moderate mucopolysaccharidosis type VI (Maroteaux-Lamy Syndrome) including two homozygous individuals with moderate phenotype (example: Voskoboeva_2022 , Zanetti _2013). These data indicate that the variant is likely to be associated with disease. Leukocyte arylsulfatase B enzyme activity from the homozygous individuals showed reduced enzymatic activity (Zanetti _2013). The following publications have been ascertained in the context of this evaluation (PMID: 23633437, 29620724, 35118118, 24243352). ClinVar contains an entry for this variant (Variation ID: 559672). Based on the evidence outlined above, the variant was classified as pathogenic.