Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001194417 | SCV001363954 | likely pathogenic | Mucopolysaccharidosis type 1 | 2019-02-05 | criteria provided, single submitter | clinical testing | Variant summary: IDUA c.1395delC (p.Gly466AlafsX59) 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 (e.g. c.1799delC (p.Ser600X), c.1861C>T (p.Arg621X)). The variant was absent in 30688 control chromosomes (gnomAD). c.1395delC has been reported in the literature in an individual affected with Mucopolysaccharidosis Type 1 (Chuang 2018). The authors of this study also performed leukocyte IDUA enzyme assays in this patient, and found a markedly decreased residual activity (Chuang 2018). 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. |
| Laboratorio de Genetica e Diagnostico Molecular, |
RCV002252326 | SCV002522974 | pathogenic | See cases | 2022-01-14 | criteria provided, single submitter | clinical testing | ACMG classification criteria: PVS1, PS4, PM2 |
| Labcorp Genetics |
RCV001194417 | SCV003786443 | pathogenic | Mucopolysaccharidosis type 1 | 2022-12-18 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 929236). This premature translational stop signal has been observed in individual(s) with mucopolysaccharidosis type I (PMID: 29801497). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change creates a premature translational stop signal (p.Gly466Alafs*59) 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). |
| Clinical Genetics Laboratory, |
RCV004697062 | SCV005198461 | likely pathogenic | not provided | 2022-05-27 | criteria provided, single submitter | clinical testing |