ClinVar Miner

Submissions for variant NM_000512.5(GALNS):c.281G>T (p.Arg94Leu)

dbSNP: rs727503946
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Total submissions: 3
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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 RCV001578280 SCV001547648 likely pathogenic 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); the prevalence of the variant in affected individuals is significantly increased compared with the prevalence in controls (PS4_moderate); absent from gnomAD v2.1.1 (PM2_moderate); multiple lines of computational evidence support a deleterious effect on the gene (PP3_supporting)
Mendelics RCV001578280 SCV002516437 pathogenic Mucopolysaccharidosis, MPS-IV-A 2022-05-04 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003323865 SCV004028767 pathogenic Morquio syndrome 2023-07-26 criteria provided, single submitter clinical testing Variant summary: GALNS c.281G>T (p.Arg94Leu) results in a non-conservative amino acid change located in the Sulfatase, N-terminal domain (IPR000917) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 247782 control chromosomes (gnomAD). c.281G>T has been reported in the literature in multiple individuals affected with Mucopolysaccharidosis Type IVA (Morquio Syndrome A) (examples: Tomatsu_2005, Morrone_2014, Bochernistan_Meta Gene_2018 ). These data indicate that the variant is very likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 24726177, 16287098). Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

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