Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000012689 | SCV000793668 | pathogenic | Hurler syndrome | 2017-08-22 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001851807 | SCV002241227 | pathogenic | Mucopolysaccharidosis type 1 | 2023-07-19 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 11914). This premature translational stop signal has been observed in individual(s) with clinical features of mucopolysaccharidosis type I (PMID: 8328452). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr64*) 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). |
| Revvity Omics, |
RCV003137513 | SCV003818233 | pathogenic | not provided | 2022-10-24 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001851807 | SCV003934353 | pathogenic | Mucopolysaccharidosis type 1 | 2023-05-25 | criteria provided, single submitter | clinical testing | Variant summary: IDUA c.192C>A (p.Tyr64X) 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. Variants downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 243844 control chromosomes (gnomAD). c.192C>A has been reported in the literature in individuals affected with Mucopolysaccharidosis Type 1 (example: Bach_1993). These data indicate that the variant may be associated with disease. The following publication has been ascertained in the context of this evaluation (PMID: 8328452). Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and all classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| OMIM | RCV000012689 | SCV000032924 | pathogenic | Hurler syndrome | 1993-08-01 | no assertion criteria provided | literature only |