Submissions for variant NM_015272.5(RPGRIP1L):c.3594G>A (p.Trp1198Ter)

dbSNP: rs1567800920

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV000785895	SCV000924471	likely pathogenic	Joubert syndrome 7	2023-01-25	criteria provided, single submitter	curation	The homozygous p.Trp1198Ter variant in RPGRIP1L was identified by our study in one individual with Joubert syndrome. The p.Trp1198Ter variant in RPGRIP1L has not been reported in individuals with Joubert syndrome 7. This variant has also been reported in ClinVar (Variation ID: 635022) and has been interpreted as likely pathogenic by the Broad Rare Disease Group. This variant was absent from large population studies. This nonsense variant leads to a premature termination codon at position 1198, which is predicted to lead to a truncated or absent protein. Loss of function of the RPGRIP1L gene is strongly associated to autosomal recessive Joubert syndrome 7. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic for Joubert syndrome 7. ACMG/AMP Criteria applied: PVS1_Strong, PM2_Supporting, PM3_Supporting (Richards 2015).
Neurology Department of Pediatrics, The Third Affiliated Hospital of Zhengzhou University	RCV000785895	SCV003802992	uncertain significance	Joubert syndrome 7		no assertion criteria provided	clinical testing