ClinVar Miner

Submissions for variant NM_001134831.2(AHI1):c.1765C>T (p.Arg589Ter) (rs267606641)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000522479 SCV000616637 pathogenic not provided 2017-10-19 criteria provided, single submitter clinical testing The R589X nonsense pathogenic variant in the AHI1 gene has been reported previously as a homozygous variant in a patient with JSRD (Valente et al., 2006). This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Functional studies in a zebrafish model demonstrate that R589X resulted in shorter cone outer segments (Lessieur et al., 2017). The R589X variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). We interpret R589X as a pathogenic variant, andhomozygosity for the R589X pathogenic variant is consistent with a diagnosis of JSRD in thisindividual. However, this result could also be seen if the patient had one allele with the R589Xpathogenic variant and one allele that was partially missing or refractory to amplification.
Ocular Genomics Institute, Massachusetts Eye and Ear RCV001376341 SCV001573456 pathogenic Rod-cone dystrophy 2021-04-08 criteria provided, single submitter research The AHI1 c.1765C>T variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we were able to apply the following criteria: PVS1 , PP1, PS3 , PP3, PM2. Based on this evidence we have classified this variant as Pathogenic.
Invitae RCV001380010 SCV001577934 pathogenic Joubert syndrome 2020-07-01 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg589*) in the AHI1 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs267606641, ExAC 0.01%). This variant has been observed to be homozygous in an individual affected with Joubert syndrome-related disorders (PMID: 16453322). ClinVar contains an entry for this variant (Variation ID: 2014). Loss-of-function variants in AHI1 are known to be pathogenic (PMID: 15322546, 16453322). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000002091 SCV000022249 pathogenic Joubert syndrome 3 2006-03-01 no assertion criteria provided literature only

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