ClinVar Miner

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

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Total submissions: 1
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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, 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.

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