Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
UW Hindbrain Malformation Research Program, |
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, |
RCV001172382 | SCV001335440 | pathogenic | Joubert syndrome with ocular defect | no assertion criteria provided | research |