ClinVar Miner

Submissions for variant NM_001134831.2(AHI1):c.2988del (p.Val997fs) (rs755246809)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000384106 SCV000330192 pathogenic not provided 2017-02-13 criteria provided, single submitter clinical testing The c.2988delA variant in the AHI1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.2988delA variant causes a frameshift starting with codon Valine 997, changes this amino acid to a Serine residue, and creates a premature Stop codon at position 20 of the new reading frame, denoted p.Val997SerfsX20. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.2988delA variant was not observed in approximately 5900 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 c.2988delA as a pathogenic variant.
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology RCV000851312 SCV000993606 likely pathogenic Joubert syndrome 3 2019-01-08 criteria provided, single submitter research
Blueprint Genetics RCV001075290 SCV001240906 likely pathogenic Retinal dystrophy 2017-11-13 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV001449700 SCV001652956 uncertain significance not specified 2020-07-13 criteria provided, single submitter clinical testing The p.Val997SerfsX20 variant in AHI1 has been reported in 1 compound heterozygous individual with Retinitis pigmentosa (Carss 2017 PMID: 28041643). It has also been identified in 0.478% (146/30560) of East Asian chromosomes, including one homozgyous observation, by gnomAD (, which is too common for the rarity and severity of Joubert syndrome. This variant is also reported in ClinVar (Variation ID: 280290). This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 997 and leads to a premature termination codon 20 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. In summary, due to conflicting evidence the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PVS1, PM3, BS1.
Al Jalila Children's Genomics Center,Al Jalila Childrens Speciality Hospital RCV001449700 SCV001984474 uncertain significance not specified 2019-12-26 criteria provided, single submitter clinical testing
NIHR Bioresource Rare Diseases, University of Cambridge RCV000504884 SCV000598927 likely pathogenic Retinitis pigmentosa 2015-01-01 no assertion criteria provided research

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