Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000807838 | SCV000947914 | pathogenic | Mucopolysaccharidosis type 1 | 2023-12-22 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 9 of the IDUA gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in IDUA are known to be pathogenic (PMID: 11735025, 21480867). 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. Disruption of this splice site has been observed in individuals with mucopolysaccharidosis (PMID: 22976768, 31194252). ClinVar contains an entry for this variant (Variation ID: 652306). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
Revvity Omics, |
RCV001784433 | SCV002023097 | pathogenic | not provided | 2021-10-25 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001784433 | SCV003852920 | likely pathogenic | not provided | 2023-03-25 | criteria provided, single submitter | clinical testing | Observed with another IDUA variant in several patients in published literature with suspected mucopolysaccharidosis type I, but it is not known whether the variants occurred on the same (in cis) or on different (in trans) chromosomes (Pollard et al., 2013; Clarke et al., 2019); Canonical splice site variant predicted to result in a null allele in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 32188113, 21480867, 11735025, 31194252, 22976768) |