Submissions for variant NM_000046.5(ARSB):c.352_365dup (p.Pro123fs)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics	RCV003333266	SCV004040633	pathogenic	Mucopolysaccharidosis type 6	2023-08-10	criteria provided, single submitter	clinical testing	A homozygous 14 base pair deletion in exon 2 of the ARSB gene that results in a frameshift and premature truncation of the protein 16 amino acids downstream to codon 123 was detected. The observed variant c.352_365dup (p.Pro123SerfsTer16) has not been reported in the 1000 genomes and gnomAD databases. The in-silico prediction of the variant is disease causing by Mutation Taster. In summary, the variant meets our criteria to be classified as pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003333266	SCV004697194	pathogenic	Mucopolysaccharidosis type 6	2023-05-19	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with ARSB-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Pro123Serfs*16) in the ARSB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ARSB are known to be pathogenic (PMID: 17458871, 22133300).