Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000208602 | SCV001577978 | pathogenic | Mucopolysaccharidosis type 1 | 2020-08-11 | criteria provided, single submitter | clinical testing | This variant results in an extension of the IDUA protein. Other variant(s) that result in a similarly extended protein product (p.*654Argext*) have been determined to be pathogenic (PMID: 29282708, 21394825). This suggests that these extensions are likely to be causative of disease. 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 create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This sequence change disrupts the translational stop signal of the IDUA mRNA. It is expected to extend the length of the IDUA protein by 55 additional amino acid residues. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with IDUA-related conditions (PMID: 7550232). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 11920). This variant has been reported to affect IDUA protein function (PMID: 7550232). |
| OMIM | RCV000012695 | SCV000032930 | pathogenic | Mucopolysaccharidosis, MPS-I-H/S | 1995-01-01 | no assertion criteria provided | literature only | |
| Gene |
RCV000208602 | SCV000264387 | not provided | Mucopolysaccharidosis type 1 | no assertion provided | literature only | Variant causes attenuated MPS I; predict extension of α-L-iduronidase at the carboxyl end that may change conformation and/or stability of enzyme. |