ClinVar Miner

Submissions for variant NM_000203.4(IDUA):c.46_57delTCGCTCCTGGCC (p.Ser16_Ala19del) (rs398123260)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000173083 SCV000224167 pathogenic not provided 2016-03-22 criteria provided, single submitter clinical testing
GeneReviews RCV000208599 SCV000264375 pathogenic Mucopolysaccharidosis type I 2016-02-11 no assertion criteria provided literature only
Integrated Genetics/Laboratory Corporation of America RCV000208599 SCV000695973 pathogenic Mucopolysaccharidosis type I 2016-06-30 criteria provided, single submitter clinical testing Variant summary: The IDUA c.46_57del12 (Ser16_Ala19del) variant result in an in frame deletion of 4 amino acids that are not located in a known functional domain of Alpha-L-iduronidase. One in silico tool predicts a benign outcome for this variant. Functional studies in cultured skin fibroblasts from patients compound heterozygous for this variant have indicated that this variant results in IDUA activity that is lower than heterozygous carriers. It has been suggested that although the precursor Ser16_Ala19del IDUA is enzymatically active, this may prevent correct post-translational processing and transport to the lysosome (Lee-Chen_J Formos Med Assoc_2002 ). This variant was absent in 6918 control chromosomes, but has been identified in many compound heterozygous MPS1 patients reported in the literature. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000208599 SCV000816966 likely pathogenic Mucopolysaccharidosis type I 2018-03-22 criteria provided, single submitter clinical testing This variant, c.46_57delTCGCTCCTGGCC, results in the deletion of 4 amino acids of the IDUA protein (p.Ser16_Ala19del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with mucopolysaccharidosis type I (PMID: 21394825, 15300847, 7951228, 15300847, 21734815). ClinVar contains an entry for this variant (Variation ID: 92643). Experimental studies have shown that this variant change results in a IDUA protein that is not cleaved post-translationally, which may prevent it's proper localization to the lysosome and interfere with it's normal function despite it's increase enzymatic activity (PMID: 12189649). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.