ClinVar Miner

Submissions for variant NM_000512.5(GALNS):c.707A>G (p.His236Arg)

dbSNP: rs398123441
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000079043 SCV000110912 uncertain significance not provided 2013-11-07 criteria provided, single submitter clinical testing
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova RCV001578306 SCV001547776 likely pathogenic Mucopolysaccharidosis, MPS-IV-A 2021-02-01 criteria provided, single submitter research The prevalence of the variant in affected individuals is significantly increased compared with the prevalence in controls (PS4_supporting); located in a mutational hot spot and/or critical and well-established functional domain without benign variation (PM1_moderate); absent from gnomAD v2.1.1 (PM2_moderate); multiple lines of computational evidence support a deleterious effect on the gene (PP3_supporting)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001731366 SCV001983494 uncertain significance not specified 2021-09-14 criteria provided, single submitter clinical testing Variant summary: GALNS c.707A>G (p.His236Arg) results in a non-conservative amino acid change located in the Sulfatase, N-terminal (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 251390 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.707A>G has been reported in the literature as a compound heterozygous genotype with c.281G>T (p.Arg94Leu) in at-least one individual affected with a confirmed molecular and biochemical diagnosis of Mucopolysaccharidosis Type IVA (Morquio Syndrome A), from Ceara state of the Northeastern region of Brazil who underwent full gene sequencing for the GALNS gene (example, Bochernistan_2018, PMID not available). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as likely pathogenic. Based on the evidence outlined above, until additional clinical/functional evidence is obtained, the variant was classified as uncertain significance.
Genome-Nilou Lab RCV001578306 SCV002044954 uncertain significance Mucopolysaccharidosis, MPS-IV-A 2021-11-07 criteria provided, single submitter clinical testing

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