ClinVar Miner

Submissions for variant NM_000512.5(GALNS):c.934A>T (p.Thr312Ser)

dbSNP: rs2142999186
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova RCV001578322 SCV001547845 uncertain significance Mucopolysaccharidosis, MPS-IV-A 2021-02-01 criteria provided, single submitter research Absent from gnomAD v2.1.1 (PM2_moderate); multiple lines of computational evidence support a deleterious effect on the gene (PP3_supporting)
Labcorp Genetics (formerly Invitae), Labcorp RCV001578322 SCV002238885 pathogenic Mucopolysaccharidosis, MPS-IV-A 2021-06-15 criteria provided, single submitter clinical testing 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. A different variant (c.935C>G) giving rise to the same protein effect has been determined to be pathogenic (PMID: 9521421, 15235041, 10814710). This suggests that this variant is also likely to be causative of disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with serine at codon 312 of the GALNS protein (p.Thr312Ser). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and serine.

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