Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000669455 | SCV000794208 | likely pathogenic | Hurler syndrome | 2017-09-20 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001192506 | SCV001360693 | likely pathogenic | Mucopolysaccharidosis type 1 | 2019-12-17 | criteria provided, single submitter | clinical testing | Variant summary: IDUA c.60_61delinsA (p.Pro22ArgfsX86) 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 was absent in 47278 control chromosomes. To our knowledge, no occurrence of c.60_61delinsA in individuals affected with Mucopolysaccharidosis Type 1 and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. However, another variant (c.65delC), causing same frameshift (p.Pro22ArgfsX86), has been reported to associate with Mucopolysaccharidosis Type 1. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Invitae | RCV001192506 | SCV004672482 | pathogenic | Mucopolysaccharidosis type 1 | 2020-03-02 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in IDUA are known to be pathogenic (PMID: 11735025, 21480867). This variant has not been reported in the literature in individuals with IDUA-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This sequence change creates a premature translational stop signal (p.Pro22Argfs*86) in the IDUA gene. It is expected to result in an absent or disrupted protein product. |