Submissions for variant NM_000046.5(ARSB):c.923G>A (p.Gly308Glu)

dbSNP: rs1554079333

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova	RCV000677608	SCV000803125	uncertain significance	Mucopolysaccharidosis type 6	2018-01-01	criteria provided, single submitter	curation	Absent from GnomAD (PM2)
Revvity Omics, Revvity	RCV000677608	SCV004234509	uncertain significance	Mucopolysaccharidosis type 6	2023-02-02	criteria provided, single submitter	clinical testing
Invitae	RCV000677608	SCV004293557	pathogenic	Mucopolysaccharidosis type 6	2023-09-20	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Gly308 amino acid residue in ARSB. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 17643332, 18406185). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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: 559825). This missense change has been observed in individual(s) with clinical features of mucopolysaccharidosis type VI (PMID: 24798265). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 308 of the ARSB protein (p.Gly308Glu).