Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory of Diagnosis and Therapy of Lysosomal Disorders, |
RCV001578458 | SCV001547943 | 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); absent from gnomAD v2.1.1 (PM2_moderate); multiple lines of computational evidence support a deleterious effect on the gene (PP3_supporting) |
| 3billion | RCV001578458 | SCV002318502 | likely pathogenic | Mucopolysaccharidosis, MPS-IV-A | 2022-03-22 | criteria provided, single submitter | clinical testing | The variant was co-segregated with Mucopolysaccharidosis IVA in multiple affected family members (PMID: 24726177). Different pathogenic/likely pathogenic amino acid change has been reported with supporting evidence at the same codon (PMID:24120057). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.933>=0.6, 3CNET: 0.96>=0.75). It is not observed in the gnomAD v2.1.1 dataset. Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline. |
| Foundation for Research in Genetics and Endocrinology, |
RCV001578458 | SCV002600895 | likely pathogenic | Mucopolysaccharidosis, MPS-IV-A | 2022-07-16 | criteria provided, single submitter | clinical testing | A Homozygous missense variation in exon 12 of the GALNS gene that results in the amino acid substitution of Proline for Argenine at codon 420 was detected. The observed variant c.1259C>G (p.Pro420Arg) has not been reported in the 1000 genomes and genomAD databases. The in silico prediction of the variant is disease causing by LRT , PROVEAN and MutationTaster2. The reference codon is conserved across species. In summary, the variant meets our criteria to be classified as likely pathogenic. In summary, the variant meets our criteria to be classified as likely pathogenic. |
| Invitae | RCV001578458 | SCV003443664 | pathogenic | Mucopolysaccharidosis, MPS-IV-A | 2023-09-10 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 420 of the GALNS protein (p.Pro420Arg). For these reasons, this variant has been classified as Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 1048357). This missense change has been observed in individual(s) with mucopolysaccharidosis type IVA (PMID: 24726177, 34387910). This variant is not present in population databases (gnomAD no frequency). |
| Molecular Biology Laboratory, |
RCV001578458 | SCV004012878 | uncertain significance | Mucopolysaccharidosis, MPS-IV-A | no assertion criteria provided | research |