Submissions for variant NM_000512.5(GALNS):c.463G>A (p.Gly155Arg)

gnomAD frequency: 0.00001  dbSNP: rs398123438

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000178783	SCV000230938	pathogenic	not provided	2013-06-13	criteria provided, single submitter	clinical testing
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova	RCV001578563	SCV001547703	pathogenic	Mucopolysaccharidosis, MPS-IV-A	2021-02-01	criteria provided, single submitter	research	In vitro and in vivo functional studies supportive of a damaging effect on the gene product (low to null enzymatic activity in homozygotes; low to null in vitro enzymatic activity; PS3_strong); the prevalence of the variant in affected individuals is significantly increased compared with the prevalence in controls (PS4_strong); very low frequency in gnomAD v2.1.1 (PM2_moderate); multiple lines of computational evidence support a deleterious effect on the gene (PP3_supporting)
CeGaT Center for Human Genetics Tuebingen	RCV000178783	SCV001747169	pathogenic	not provided	2021-04-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001578563	SCV002045025	pathogenic	Mucopolysaccharidosis, MPS-IV-A	2021-11-07	criteria provided, single submitter	clinical testing
Genetics and Molecular Pathology, SA Pathology	RCV002272058	SCV002556967	pathogenic	Skeletal dysplasia	2021-10-21	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV001578563	SCV003832540	likely pathogenic	Mucopolysaccharidosis, MPS-IV-A	2022-04-04	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000178783	SCV004226684	pathogenic	not provided	2023-02-15	criteria provided, single submitter	clinical testing	PP3, PP4, PM2, PM3_strong, PS4_moderate
Invitae	RCV001578563	SCV004296416	pathogenic	Mucopolysaccharidosis, MPS-IV-A	2023-12-17	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 155 of the GALNS protein (p.Gly155Arg). This variant is present in population databases (rs398123438, gnomAD 0.006%). This missense change has been observed in individual(s) with mucopolysaccharidosis type IVA (PMID: 24120057, 32024277). ClinVar contains an entry for this variant (Variation ID: 93178). 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 GALNS protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.