ClinVar Miner

Submissions for variant NM_000168.6(GLI3):c.1464_1489dup (p.Leu497fs) (rs1554314581)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000486221 SCV000567461 pathogenic not provided 2015-07-20 criteria provided, single submitter clinical testing The c.1464_1489dup26 duplication in the GLI3 gene has not been reported previously as a pathogenic variant nor as a benign polymorphism, to our knowledge. The c.1464_1489dup26 variant causes a frameshift starting with codon Leucine 497, changes this amino acid to an Arginine residue, and creates a premature Stop codon at position 14 of the new reading frame, denoted p.Leu497ArgfsX14. This duplication is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Frameshift and other protein truncating variant downstream of this duplication have been reported in the Human Gene Mutation Database in association with GLI3-related disorders (Stenson et al., 2014), supporting the pathogenicity of more upstream truncating variants. The c.1464_1489dup26 duplication was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.1464_1489dup26 as a pathogenic variant.

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.