Submissions for variant NM_000046.5(ARSB):c.960C>G (p.Ser320Arg)

dbSNP: rs762614315

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000493516	SCV000582894	likely pathogenic	not provided	2016-06-15	criteria provided, single submitter	clinical testing	The S320R variant has previously been reported in association with mucopolysaccharidosis VI (MPSVI) in an individual who was homozygous for S320R and another individual who was compound heterozygous for S320R and a frameshift variant in ARSB (Litjens et al., 2001; Uttarilli et al., 2015). The S320R variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants in nearby residues (R315Q, L321P, G324V) have been reported in the Human Gene Mutation Database in association with MPSVI (Stenson et al., 2014), supporting the functional importance of this region of the protein.] Therefore, we interpret S320R to be a likely pathogenic variant.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000677613	SCV002232246	pathogenic	Mucopolysaccharidosis type 6	2023-08-02	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects ARSB function (PMID: 27826022). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ARSB protein function. ClinVar contains an entry for this variant (Variation ID: 430162). This missense change has been observed in individual(s) with mucopolysaccharidosis type VI (PMID: 10923267, 11668612, 26609033). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 320 of the ARSB protein (p.Ser320Arg).
Revvity Omics, Revvity	RCV000677613	SCV004238472	likely pathogenic	Mucopolysaccharidosis type 6	2023-06-02	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000677613	SCV005056598	pathogenic	Mucopolysaccharidosis type 6	2023-12-30	criteria provided, single submitter	clinical testing
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova	RCV000677613	SCV000803131	uncertain significance	Mucopolysaccharidosis type 6	2018-01-01	flagged submission	curation	Absent from GnomAD (PM2); Multiple lines of computational evidence support a deleterious effect on the gene product (PP3)