Submissions for variant NM_001174150.2(ARL13B):c.246del (p.Ile81_Trp82insTer)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002308659	SCV002600710	likely pathogenic	Joubert syndrome and related disorders	2022-10-24	criteria provided, single submitter	clinical testing	Variant summary: ARL13B c.246delG (p.Trp82X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251214 control chromosomes (gnomAD). To our knowledge, no occurrence of c.246delG in individuals affected with Joubert Syndrome And Related Disorders has been reported. However, a different variant causing the same amino acid effect (c.246G>A, p.Trp82X) has been reported in the literature in individuals affected with Joubert Syndrome (PMIDs: 18674751, 26092869). Experimental evidence demonstrated p.Trp82X affects protein function (e.g. Higginbotham_2012, Li_2016, Guo_2019). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.