NM_001134831.2(AHI1):c.2687A>G (p.His896Arg) AND Agenesis of cerebellar vermis

Clinical significance:Uncertain significance (Last evaluated: Jun 5, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_001134831.2(AHI1):c.2687A>G (p.His896Arg)]

NM_001134831.2(AHI1):c.2687A>G (p.His896Arg)

AHI1:Abelson helper integration site 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_001134831.2(AHI1):c.2687A>G (p.His896Arg)
  • NC_000006.12:g.135427244T>C
  • NG_008643.2:g.75522A>G
  • NM_001134830.2:c.2687A>G
  • NM_001134831.2:c.2687A>GMANE SELECT
  • NM_001134832.2:c.2687A>G
  • NM_001350503.2:c.2687A>G
  • NM_001350504.2:c.2687A>G
  • NM_017651.4:c.2687A>G
  • NM_017651.5:c.2687A>G
  • NP_001128302.1:p.His896Arg
  • NP_001128303.1:p.His896Arg
  • NP_001128304.1:p.His896Arg
  • NP_001337432.1:p.His896Arg
  • NP_001337433.1:p.His896Arg
  • NP_060121.3:p.His896Arg
  • NP_060121.3:p.His896Arg
  • NC_000006.11:g.135748382T>C
  • NM_001134831.1:c.2687A>G
  • Q8N157:p.His896Arg
Protein change:
UniProtKB: Q8N157#VAR_076822; dbSNP: rs863225135
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_001134830.2:c.2687A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001134831.2:c.2687A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001134832.2:c.2687A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350503.2:c.2687A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350504.2:c.2687A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_017651.4:c.2687A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_017651.5:c.2687A>G - missense variant - [Sequence Ontology: SO:0001583]


Agenesis of cerebellar vermis (JBTS)
CEREBELLOPARENCHYMAL DISORDER IV; Joubert syndrome; Cerebelloparenchymal disorder 4; See all synonyms [MedGen]
MONDO: MONDO:0018772; MedGen: C0431399; Orphanet: 475; OMIM: PS213300; Human Phenotype Ontology: HP:0002335

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV001413119Invitaecriteria provided, single submitter
Uncertain significance
(Jun 5, 2020)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing



AHI1 mutations cause both retinal dystrophy and renal cystic disease in Joubert syndrome.

Parisi MA, Doherty D, Eckert ML, Shaw DW, Ozyurek H, Aysun S, Giray O, Al Swaid A, Al Shahwan S, Dohayan N, Bakhsh E, Indridason OS, Dobyns WB, Bennett CL, Chance PF, Glass IA.

J Med Genet. 2006 Apr;43(4):334-9. Epub 2005 Sep 9.

PubMed [citation]

Missense mutations in the WD40 domain of AHI1 cause non-syndromic retinitis pigmentosa.

Nguyen TT, Hull S, Roepman R, van den Born LI, Oud MM, de Vrieze E, Hetterschijt L, Letteboer SJF, van Beersum SEC, Blokland EA, Yntema HG, Cremers FPM, van der Zwaag PA, Arno G, van Wijk E, Webster AR, Haer-Wigman L.

J Med Genet. 2017 Sep;54(9):624-632. doi: 10.1136/jmedgenet-2016-104200. Epub 2017 Apr 25.

PubMed [citation]
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001413119.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)


This sequence change replaces histidine with arginine at codon 896 of the AHI1 protein (p.His896Arg). The histidine residue is moderately conserved and there is a small physicochemical difference between histidine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with Joubert syndrome or non-syndromic retinal dystrophy (PMID: 16155189, 28442542). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 217532). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 27, 2021

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