ClinVar Miner

Submissions for variant NM_000512.5(GALNS):c.251C>A (p.Ala84Glu)

dbSNP: rs141340188
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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 RCV001578544 SCV001547634 uncertain significance Mucopolysaccharidosis, MPS-IV-A 2021-02-01 criteria provided, single submitter research In vivo functional studies supportive of a damaging effect on the gene product (low to null enzymatic activity in homozygotes; PS3_supporting); very low frequency in 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 RCV001578544 SCV002270262 pathogenic Mucopolysaccharidosis, MPS-IV-A 2023-08-04 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 84 of the GALNS protein (p.Ala84Glu). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with mucopolysaccharidosis type IVA (PMID: 24726177, 34387910). ClinVar contains an entry for this variant (Variation ID: 1048443). 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. For these reasons, this variant has been classified as Pathogenic.

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