Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002302466 | SCV002598625 | likely pathogenic | Mucopolysaccharidosis type 6 | 2022-09-12 | criteria provided, single submitter | clinical testing | Variant summary: The variant identified by MLPA or other technology involves the duplication of exon 5 in the ARSB gene. A presumed nomenclature of c.(898+1_899-1)_(1142+1_1143-1)dup has been designated for the purposes of this classification. It has been assumed that this is a tandem duplication in direct orientation (Richardson_GIM_2018, Newman_AJHG_2015). Although exact breakpoints of this duplication are not known, it is expected to result in a frameshift in the ARSB gene, a known mechanism of disease. The variant allele was found at a frequency of 0.00014 in 21694 control chromosomes (gnomAD, Structural Variants dataset). To our knowledge, no occurrence of c.(898+1_899-1)_(1142+1_1143-1)dup in individuals affected with Mucopolysaccharidosis Type VI (Maroteaux-Lamy Syndrome) and no experimental evidence demonstrating its impact on protein function have been reported in the literature. A ClinVar submitter (evaluation after 2014) cites the variant as likely pathogenic reporting internal evidence of a similar copy number variant observed in individual(s) with a biochemical diagnosis of Maroteaux-Lamy syndrome VI (SCV000963358.3). Based on the evidence outlined above, the variant was classified as likely pathogenic. |