Submissions for variant NM_000046.5(ARSB):c.753C>G (p.Tyr251Ter)

dbSNP: rs765711776

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000579253	SCV000680732	pathogenic	not provided	2019-05-01	criteria provided, single submitter	clinical testing	Not observed in large population cohorts (Lek et al., 2016); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 30118150, 28914427, 23430861, 27629047, 24798265, 31009684, 29620724)
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova	RCV000677594	SCV000803111	pathogenic	Mucopolysaccharidosis type 6	2018-01-01	criteria provided, single submitter	curation	Nonsense variant (PVS1); 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); Reputable source identifies as pathogenic (PP5)
Invitae	RCV000677594	SCV000937682	pathogenic	Mucopolysaccharidosis type 6	2018-08-11	criteria provided, single submitter	clinical testing	This variant is not present in population databases (ExAC no frequency). For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in ARSB are known to be pathogenic (PMID: 17458871, 22133300). This variant has been observed in an individual affected with mucopolysaccharidosis type VI (PMID: 23430861). ClinVar contains an entry for this variant (Variation ID: 488822). This sequence change creates a premature translational stop signal (p.Tyr251*) in the ARSB gene. It is expected to result in an absent or disrupted protein product.
CeGaT Center for Human Genetics Tuebingen	RCV000579253	SCV001371503	pathogenic	not provided	2020-05-01	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000677594	SCV002018863	pathogenic	Mucopolysaccharidosis type 6	2021-01-13	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000677594	SCV004202312	pathogenic	Mucopolysaccharidosis type 6	2021-12-04	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV000677594	SCV005038867	pathogenic	Mucopolysaccharidosis type 6	2024-03-14	criteria provided, single submitter	clinical testing
Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City	RCV000677594	SCV001133218	pathogenic	Mucopolysaccharidosis type 6	2019-09-26	no assertion criteria provided	clinical testing
Natera, Inc.	RCV000677594	SCV001457626	pathogenic	Mucopolysaccharidosis type 6	2020-09-16	no assertion criteria provided	clinical testing