Submissions for variant NM_000046.5(ARSB):c.1178A>G (p.His393Arg)

dbSNP: rs118203944

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000677460	SCV002228308	pathogenic	Mucopolysaccharidosis type 6	2022-08-06	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.His393 amino acid residue in ARSB. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 8651289, 11939792, 17458871). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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: 559686). This missense change has been observed in individual(s) with mucopolysaccharidosis type VI (PMID: 26609033). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 393 of the ARSB protein (p.His393Arg).
Baylor Genetics	RCV000677460	SCV004209892	pathogenic	Mucopolysaccharidosis type 6	2023-03-13	criteria provided, single submitter	clinical testing
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova	RCV000677460	SCV000802967	uncertain significance	Mucopolysaccharidosis type 6	2018-01-01	flagged submission	curation	Absent from GnomAD (PM2)