Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000779749 | SCV000916524 | likely pathogenic | Metachromatic leukodystrophy | 2018-04-16 | criteria provided, single submitter | clinical testing | Variant summary: ARSB c.219_230delinsG (p.Asp73GlufsX50) 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. A truncation downstream of this position has been classified as pathogenic by our laboratory, c.427delG (p.Val143fsX41). The variant was absent in 210748 control chromosomes (gnomAD). The variant, c.219_230delinsG, has been reported in the literature in one compound heterozygous individual affected with severe Mucopolysaccharidosis Type VI (Maroteaux-Lamy Syndrome)(Isbrandt_1996). This publication, Isbrandt_1996, also reports experimental evidence showing a lack of ARSB mRNA in the patient's fibroblasts, though the data was not presented for review. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. |