ClinVar Miner

Submissions for variant NM_001134831.2(AHI1):c.2212C>T (p.Arg738Ter)

gnomAD frequency: 0.00003  dbSNP: rs372659908
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
UW Hindbrain Malformation Research Program,University of Washington RCV000201604 SCV000256249 pathogenic Joubert syndrome 3 2015-02-23 criteria provided, single submitter research
GeneDx RCV000255574 SCV000322104 pathogenic not provided 2018-10-02 criteria provided, single submitter clinical testing A pathogenic variant has been identified in the AHI1 gene. The R738X variant has been reported previously in multiple individuals with JSRD who had a second AHI1 variant on the opposite allele (in trans) in published literature (Parisi et al., 2006; Valente et al., 2006; Bachmann-Gagescu et al., 2015). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. It is not observed at a significant frequency in large population cohorts (Lek et al., 2016). We interpret R738X as a pathogenic variant.
Invitae RCV001387494 SCV001588141 pathogenic Joubert syndrome 2021-12-17 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg738*) 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 present in population databases (rs372659908, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with Joubert syndrome or related conditions (PMID: 16453322, 21866095, 26092869). ClinVar contains an entry for this variant (Variation ID: 217525). For these reasons, this variant has been classified as Pathogenic.
Sharon lab,Hadassah-Hebrew University Medical Center RCV001002863 SCV001160890 pathogenic Retinitis pigmentosa 2019-06-23 no assertion criteria provided research

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