Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory of Diagnosis and Therapy of Lysosomal Disorders, |
RCV001578330 | SCV001547903 | pathogenic | Mucopolysaccharidosis, MPS-IV-A | 2021-02-01 | criteria provided, single submitter | research | Frameshift variant (PVS1_very strong); 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_strong); very low frequency in gnomAD v2.1.1 (PM2_moderate) |
| Labcorp Genetics |
RCV001578330 | SCV002243347 | pathogenic | Mucopolysaccharidosis, MPS-IV-A | 2023-12-09 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Pro381Leufs*10) in the GALNS gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GALNS are known to be pathogenic (PMID: 12442278). This variant is present in population databases (rs746086649, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with mucopolysaccharidosis type IVA (PMID: 22521955). ClinVar contains an entry for this variant (Variation ID: 1048228). For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002222703 | SCV002500792 | pathogenic | Morquio syndrome | 2022-03-31 | criteria provided, single submitter | clinical testing | Variant summary: GALNS c.1142delC (p.Pro381LeufsX10) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 1.6e-05 in 248822 control chromosomes. c.1142delC has been reported in the literature in individuals affected with Mucopolysaccharidosis Type IVA (Morquio Syndrome A; eg. Pajares_2012, Morrone_2014). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Revvity Omics, |
RCV001578330 | SCV004236687 | pathogenic | Mucopolysaccharidosis, MPS-IV-A | 2023-04-05 | criteria provided, single submitter | clinical testing |