Submissions for variant NM_000046.5(ARSB):c.1601A>G (p.Ter534Trp)

dbSNP: rs1554069655

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Revvity Omics, Revvity	RCV000677504	SCV002021449	likely pathogenic	Mucopolysaccharidosis type 6	2021-07-23	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000677504	SCV003525875	pathogenic	Mucopolysaccharidosis type 6	2022-07-05	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant results in an extension of the ARSB protein. Other variant(s) that result in a similarly extended protein product (p.*534Serext*50 and p.*534Glnext*50) have been determined to be pathogenic (PMID: 8144552; Invitae). This suggests that these extensions are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 559729). This variant is also known as p.*534W. This variant has been observed in individual(s) with mucopolysaccharidosis type VI (PMID: 26909334, 30524696). This variant is not present in population databases (gnomAD no frequency). This sequence change results in a frameshift in the ARSB gene (p.*534Trpext*50). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last amino acid(s) of the ARSB protein and extend the protein by 50 additional amino acid residues
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova	RCV000677504	SCV000803014	uncertain significance	Mucopolysaccharidosis type 6	2018-01-01	flagged submission	curation	Absent from GnomAD (PM2); Protein length changes as a result of a stop-loss variant (PM4)