Submissions for variant NM_001134831.2(AHI1):c.1051C>T (p.Arg351Ter)

dbSNP: rs121434348

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001058641	SCV001223227	pathogenic	Familial aplasia of the vermis	2024-02-19	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg351*) in the AHI1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in AHI1 are known to be pathogenic (PMID: 15322546, 16453322, 28442542, 29186038). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Joubert syndrome (PMID: 15322546). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 2010). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Kids Neuroscience Centre, Sydney Children's Hospitals Network	RCV000002087	SCV001571488	pathogenic	Joubert syndrome 3		criteria provided, single submitter	provider interpretation	Observed in conjunction with c.2492+5G>A (induces abnormal splicing); compound heterozygous variants in AHI1 are consistent with autosomal recessive Joubert syndrome. This has also been previously reported as Pathogenic (VCV000002010)
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	RCV000002087	SCV004801225	pathogenic	Joubert syndrome 3	2024-03-14	criteria provided, single submitter	research
OMIM	RCV000002087	SCV000022245	pathogenic	Joubert syndrome 3	2004-09-01	no assertion criteria provided	literature only