Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Medical Molecular Genetics Department, |
RCV000656129 | SCV000609483 | pathogenic | Mucopolysaccharidosis type 6 | 2015-12-01 | criteria provided, single submitter | research | |
| Laboratory of Diagnosis and Therapy of Lysosomal Disorders, |
RCV000656129 | SCV000803083 | pathogenic | Mucopolysaccharidosis type 6 | 2018-01-01 | criteria provided, single submitter | curation | Nonsense variant (PVS1); In vitro functional studies supportive of a damaging effect on the gene product (low to no ARSB activity in homozygotes; PS3); Very low frequency in ExAC (PM2) |
| Labcorp Genetics |
RCV000656129 | SCV002240372 | pathogenic | Mucopolysaccharidosis type 6 | 2023-12-15 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg160*) in the ARSB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ARSB are known to be pathogenic (PMID: 17458871, 22133300). This variant is present in population databases (no rsID available, gnomAD 0.002%). This premature translational stop signal has been observed in individual(s) with ARSB-related conditions (PMID: 8125475, 33163362). ClinVar contains an entry for this variant (Variation ID: 445291). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000656129 | SCV002511470 | pathogenic | Mucopolysaccharidosis type 6 | 2022-04-11 | criteria provided, single submitter | clinical testing | Variant summary: ARSB c.478C>T (p.Arg160X) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 8e-06 in 251472 control chromosomes. c.478C>T has been reported in the literature in individuals affected with Mucopolysaccharidosis Type VI (Maroteaux-Lamy Syndrome) (example, Garrido_2007, Jurecka_2012). Three 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. |
| Baylor Genetics | RCV000656129 | SCV004209069 | pathogenic | Mucopolysaccharidosis type 6 | 2024-03-07 | criteria provided, single submitter | clinical testing | |
| Victorian Clinical Genetics Services, |
RCV000656129 | SCV005087214 | pathogenic | Mucopolysaccharidosis type 6 | 2023-07-16 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with mucopolysaccharidosis type VI (Maroteaux-Lamy) (MIM#253200). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0115 - Variants in this gene are known to have variable expressivity. Age of onset, rate of disease progression, and clinical manifestations vary widely among individuals (PMID: 30118150). (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0252 - This variant is homozygous. (I) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (v2 & v3: 5 heterozygotes, 0 homozygotes). (SP) 0701 - Other variants predicted to result in NMD comparable to the one identified in this case have very strong previous evidence for pathogenicity (DECIPHER). (SP) 0801 - This variant has very strong previous evidence of pathogenicity in unrelated individuals. It has been reported as pathogenic in ClinVar and detected in multiple families with Maroteaux-Lamy syndrome (MPS VI). (SP) 1209 - This variant has been shown to be both maternally and paternally inherited (biallelic) (by segregation analysis in an external laboratory). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |