ClinVar Miner

Submissions for variant NM_001134831.2(AHI1):c.1267C>T (p.Gln423Ter) (rs777668842)

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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 RCV000201715 SCV000256247 pathogenic Joubert syndrome 3 2015-02-23 criteria provided, single submitter research
Invitae RCV000206729 SCV000259658 pathogenic Joubert syndrome 2018-12-20 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln423*) in the AHI1 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs777668842, ExAC 0.01%). This variant has been reported in a number of unrelated individuals with Joubert syndrome or Joubert syndrome-related disorders (PMID: 16155189, 16453322, 26092869). All of these individuals were either homozygous for p.Gln423* or compound heterozygous with a second truncating variant. ClinVar contains an entry for this variant (Variation ID: 217523). Loss-of-function variants in AHI1 are known to be pathogenic (PMID: 15322546, 16453322). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000482493 SCV000567666 pathogenic not provided 2015-09-07 criteria provided, single submitter clinical testing The Q423X pathogenic variant in the AHI1 gene has been reported previously in multiple unrelated individuals with Joubert syndrome and was observed in either the homozygous state or in the heterozygous state with a second heterozygous loss-of-function variant present in all reported individuals (Valente et al., 2006; Parisi et al., 2006; Chaki et al., 2011). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The Q423X variant was not observed in approximately 5,900 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret Q423X as a pathogenic variant.
Blueprint Genetics RCV001074545 SCV001240136 pathogenic Retinal dystrophy 2018-03-13 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000482493 SCV001247115 pathogenic not provided 2017-07-01 criteria provided, single submitter clinical testing

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