ClinVar Miner

Submissions for variant NM_000512.5(GALNS):c.1219A>C (p.Asn407His) (rs749578474)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV000784908 SCV000923449 likely pathogenic Mucopolysaccharidosis, MPS-IV-A 2019-01-01 criteria provided, single submitter clinical testing
Invitae RCV000784908 SCV001406876 likely pathogenic Mucopolysaccharidosis, MPS-IV-A 2019-08-13 criteria provided, single submitter clinical testing This sequence change replaces asparagine with histidine at codon 407 of the GALNS protein (p.Asn407His). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and histidine. This variant is present in population databases (rs749578474, ExAC 0.002%). This variant has been observed in the homozygous state or in combination with another GALNS variant in individuals with Morquio syndrome (MPSIVA) (PMID: 9298823, 29275451). ClinVar contains an entry for this variant (Variation ID: 634437). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Tolerated; PolyPhen-2: Possibly Damaging; Align-GVGD: Class C0). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Laboratory of Diagnosis and Therapy of Lysosomal Disorders,University of Padova RCV000784908 SCV001547932 likely pathogenic Mucopolysaccharidosis, MPS-IV-A 2021-02-01 criteria provided, single submitter curation The prevalence of the variant in affected individuals is significantly increased compared with the prevalence in controls (PS4_strong); very low frequency in gnomAD v2.1.1 (PM2_moderate)

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