Submissions for variant NM_000512.5(GALNS):c.562G>A (p.Gly188Ser)

dbSNP: rs2143002317

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	RCV001578511	SCV001547740	uncertain significance	Mucopolysaccharidosis, MPS-IV-A	2021-02-01	criteria provided, single submitter	curation	In vivo functional studies supportive of a damaging effect on the gene product (low to null enzymatic activity in homozygotes; PS3_supporting); absent from gnomAD v2.1.1 (PM2_moderate); multiple lines of computational evidence support a deleterious effect on the gene (PP3_supporting)
Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India	RCV001578511	SCV002507142	likely pathogenic	Mucopolysaccharidosis, MPS-IV-A		criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001578511	SCV004296414	pathogenic	Mucopolysaccharidosis, MPS-IV-A	2023-03-02	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 188 of the GALNS protein (p.Gly188Ser). For these reasons, this variant has been classified as Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 1048406). This missense change has been observed in individual(s) with Clinical features of Mucopolysaccharidosis type IVA (PMID: 25252036). This variant is not present in population databases (gnomAD no frequency).