Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000178107 | SCV000230107 | pathogenic | not provided | 2015-02-05 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV000282371 | SCV000399654 | likely pathogenic | Mucopolysaccharidosis, MPS-IV-A | 2017-04-28 | criteria provided, single submitter | clinical testing | The GALNS c.421T>A (p.Trp141Arg) missense variant has been reported in two studies in which it was identified in a homozygous state in two patients with mucopolysaccharidosis type IV, both exhibiting a severe phenotype (Bunge et al. 1997; Khedhiri et al. 2014). The p.Trp141Arg variant was absent from the 116 control chromosomes and is not observed in the 1000 Genomes Project, the Exome Sequencing Project, or the Exome Aggregation Consortium in an area of good sequence coverage, suggesting it is rare. Negligible GALNS activity was observed in leukocytes extracted from one of the patients (Khedhiri et al. 2014). The Trp141 residue is well-conserved. Structural studies of the 3D structure of human GALNS demonstrated that the residue is located in the hydrophobic core of the enzyme near the active site (Rivera-Colón et al. 2012). Based on the available evidence, the p.Trp141Arg variant is classified as likely pathogenic for mucopolysaccharidosis type IV. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, |
RCV000282371 | SCV001547683 | uncertain significance | Mucopolysaccharidosis, MPS-IV-A | 2021-02-01 | criteria provided, single submitter | curation | 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_supporting); absent from gnomAD v2.1.1 (PM2_moderate); multiple lines of computational evidence support a deleterious effect on the gene (PP3_supporting) |
Genome- |
RCV000282371 | SCV002044963 | likely pathogenic | Mucopolysaccharidosis, MPS-IV-A | 2021-11-07 | criteria provided, single submitter | clinical testing |