Submissions for variant NM_001134831.2(AHI1):c.2168G>A (p.Arg723Gln) (rs121434351)

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Total submissions: 5

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
UW Hindbrain Malformation Research Program,University of Washington	RCV000002092	SCV000256255	pathogenic	Joubert syndrome 3	2015-02-23	criteria provided, single submitter	research
Invitae	RCV000463110	SCV000547169	likely pathogenic	Joubert syndrome	2019-11-26	criteria provided, single submitter	clinical testing	This sequence change replaces arginine with glutamine at codon 723 of the AHI1 protein (p.Arg723Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs121434351, ExAC 0.009%). This variant has been observed in individual(s) with Joubert syndrome (PMID: 16453322, 26092869). It has also been observed to segregate with disease in related individuals. This variant has been reported to affect AHI1 protein function (PMID: 21623382). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
SIB Swiss Institute of Bioinformatics	RCV000002092	SCV000803621	likely pathogenic	Joubert syndrome 3	2018-05-31	criteria provided, single submitter	curation	This variant is interpreted as a Likely Pathogenic, for Joubert syndrome, in Autosomal Recessive manner. The following ACMG Tag(s) were applied: PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PS3 => Well-established functional studies show a deleterious effect (PMID:21623382).
OMIM	RCV000002092	SCV000022250	pathogenic	Joubert syndrome 3	2006-03-01	no assertion criteria provided	literature only
Laboratory of Genetics in Ophthalmology,Institut Imagine	RCV001172382	SCV001335440	pathogenic	Joubert syndrome with ocular defect		no assertion criteria provided	research

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