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NM_001134831.2(AHI1):c.2168G>A (p.Arg723Gln) AND Joubert syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 6, 2025
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000463110.8

Allele description [Variation Report for NM_001134831.2(AHI1):c.2168G>A (p.Arg723Gln)]

NM_001134831.2(AHI1):c.2168G>A (p.Arg723Gln)

Gene:
AHI1:Abelson helper integration site 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
6q23.3
Genomic location:
Preferred name:
NM_001134831.2(AHI1):c.2168G>A (p.Arg723Gln)
Other names:
NM_001134830.1(AHI1):c.2168G>A(p.Arg723Gln); NM_001134831.1(AHI1):c.2168G>A(p.Arg723Gln); NM_001134832.1(AHI1):c.2168G>A(p.Arg723Gln); NM_017651.4(AHI1):c.2168G>A(p.Arg723Gln); NM_001134831.2(AHI1):c.2168G>A
HGVS:
  • NC_000006.12:g.135433125C>T
  • NG_008643.2:g.69641G>A
  • NM_001134830.2:c.2168G>A
  • NM_001134831.2:c.2168G>AMANE SELECT
  • NM_001134832.2:c.2168G>A
  • NM_001350503.2:c.2168G>A
  • NM_001350504.2:c.2168G>A
  • NM_017651.5:c.2168G>A
  • NP_001128302.1:p.Arg723Gln
  • NP_001128303.1:p.Arg723Gln
  • NP_001128304.1:p.Arg723Gln
  • NP_001337432.1:p.Arg723Gln
  • NP_001337433.1:p.Arg723Gln
  • NP_060121.3:p.Arg723Gln
  • NP_060121.3:p.Arg723Gln
  • NC_000006.11:g.135754263C>T
  • NM_001134831.1:c.2168G>A
  • NM_017651.4:c.2168G>A
  • Q8N157:p.Arg723Gln
Protein change:
R723Q; ARG723GLN
Links:
UniProtKB: Q8N157#VAR_037894; OMIM: 608894.0006; dbSNP: rs121434351
NCBI 1000 Genomes Browser:
rs121434351
Molecular consequence:
  • NM_001134830.2:c.2168G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001134831.2:c.2168G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001134832.2:c.2168G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350503.2:c.2168G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350504.2:c.2168G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_017651.5:c.2168G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Joubert syndrome
Synonyms:
CEREBELLOPARENCHYMAL DISORDER IV; JOUBERT-BOLTSHAUSER SYNDROME; Familial aplasia of the vermis
Identifiers:
MONDO: MONDO:0018772; MedGen: C0431399; Orphanet: 475; OMIM: PS213300

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000547169Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jan 6, 2025) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

AHI1 gene mutations cause specific forms of Joubert syndrome-related disorders.

Valente EM, Brancati F, Silhavy JL, Castori M, Marsh SE, Barrano G, Bertini E, Boltshauser E, Zaki MS, Abdel-Aleem A, Abdel-Salam GM, Bellacchio E, Battini R, Cruse RP, Dobyns WB, Krishnamoorthy KS, Lagier-Tourenne C, Magee A, Pascual-Castroviejo I, Salpietro CD, Sarco D, Dallapiccola B, et al.

Ann Neurol. 2006 Mar;59(3):527-34.

PubMed [citation]
PMID:
16453322

Joubert syndrome: a model for untangling recessive disorders with extreme genetic heterogeneity.

Bachmann-Gagescu R, Dempsey JC, Phelps IG, O'Roak BJ, Knutzen DM, Rue TC, Ishak GE, Isabella CR, Gorden N, Adkins J, Boyle EA, de Lacy N, O'Day D, Alswaid A, Ramadevi A R, Lingappa L, Lourenço C, Martorell L, Garcia-Cazorla À, Ozyürek H, Haliloğlu G, Tuysuz B, et al.

J Med Genet. 2015 Aug;52(8):514-22. doi: 10.1136/jmedgenet-2015-103087. Epub 2015 Jun 19.

PubMed [citation]
PMID:
26092869
PMCID:
PMC5082428
See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000547169.8

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 723 of the AHI1 protein (p.Arg723Gln). This variant is present in population databases (rs121434351, gnomAD 0.009%). This missense change has been observed in individual(s) with Joubert syndrome (PMID: 16453322, 26092869; internal data). ClinVar contains an entry for this variant (Variation ID: 2015). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt AHI1 protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects AHI1 function (PMID: 21623382). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: May 25, 2025