Description
Variant summary: IDUA c.326_331delACAACT (p.Tyr109_Asn110del) results in an in-frame deletion that is predicted to remove 2 amino acids from the encoded protein. The variant allele was found at a frequency of 4e-06 in 250358 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.326_331delACAACT in individuals affected with Mucopolysaccharidosis Type 1 and no experimental evidence demonstrating its impact on protein function have been reported. However, missense variants affecting the residues that are deleted by this variant have been reported in Mucopolysaccharidosis Type 1 patients in the literature; i.e. in 5 homozygotes with Y109H, who had intermediate (Hurler-Scheie syndrome) phenotype (Taghikhani_2019), and 2 in compound heterozygous patients with the N110D/Q70X genotype, who had severe (Hurler syndrome) phenotype (Clarke_2019). These reports suggest that other variants altering these residues might be also associated with disease. In addition, the N110 residue, was reported as a protein glycosylation site (e.g. Maita_2013, Bie_2013). The following publications have been ascertained in the context of this evaluation (PMID: 31386236, 31194252, 23959878 , 24036510). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014, and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
| # | Sample | Method | Observation |
|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
|---|
| 1 | germline | unknown | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |
