Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001236736 | SCV001409472 | pathogenic | Mucopolysaccharidosis type 1 | 2022-02-02 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with IDUA-related conditions. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 962814). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Thr103Leufs*5) in the IDUA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in IDUA are known to be pathogenic (PMID: 11735025, 21480867). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001236736 | SCV002572158 | likely pathogenic | Mucopolysaccharidosis type 1 | 2022-08-19 | criteria provided, single submitter | clinical testing | Variant summary: IDUA c.306delC (p.Thr103LeufsX5) 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 250140 control chromosomes (gnomAD). To our knowledge, no occurrence of c.306delC in individuals affected with Mucopolysaccharidosis Type 1 and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted a clinical-significance assessment 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. |