ClinVar Miner

Submissions for variant NM_015272.5(RPGRIP1L):c.2992del (p.Ile998fs) (rs767018622)

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
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000609113 SCV000712203 likely pathogenic Joubert syndrome 2016-06-06 criteria provided, single submitter clinical testing The p.Ile998PhefsX5 variant in RPGRIP1L has not been previously reported in the literature. It has been identified in 1/120,760 of chromosomes by the Exome Aggr egation Consortium (ExAC, http://exac.broadinstitute.org). This variant is predi cted to cause a frameshift, which alters the protein?s amino acid sequence begin ning at position 998 and leads to a premature termination codon 5 amino acids do wnstream. This alteration is then predicted to lead to a truncated or absent pro tein. Complete loss of RPGRIP1L function is an established disease mechanism in RPGRIP1L-related disorders such as Joubert syndrome and Meckel syndrome (Delous 2007). Moreover, Rpgrip1l -/- mice show a similar phenotype to individuals affec ted with these disorders including polydactyly, craniofacial malformations, and left-right symmetry defects (Vierkotten 2007). In summary, although additional studies are required to fully establish its clinical significance, the p.Ile998P hefsX5 variant is 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.