NM_001134831.2(AHI1):c.1904C>T (p.Pro635Leu) AND Joubert syndrome

Clinical significance:Uncertain significance (Last evaluated: Feb 2, 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.1904C>T (p.Pro635Leu)]

NM_001134831.2(AHI1):c.1904C>T (p.Pro635Leu)

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.1904C>T (p.Pro635Leu)
  • NC_000006.12:g.135442590G>A
  • NG_008643.2:g.60176C>T
  • NM_001134830.2:c.1904C>T
  • NM_001134831.2:c.1904C>TMANE SELECT
  • NM_001134832.2:c.1904C>T
  • NM_001350503.2:c.1904C>T
  • NM_001350504.2:c.1904C>T
  • NM_017651.5:c.1904C>T
  • NP_001128302.1:p.Pro635Leu
  • NP_001128303.1:p.Pro635Leu
  • NP_001128304.1:p.Pro635Leu
  • NP_001337432.1:p.Pro635Leu
  • NP_001337433.1:p.Pro635Leu
  • NP_060121.3:p.Pro635Leu
  • NP_060121.3:p.Pro635Leu
  • NC_000006.11:g.135763728G>A
  • NM_017651.4:c.1904C>T
Protein change:
dbSNP: rs371531507
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_001134830.2:c.1904C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001134831.2:c.1904C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001134832.2:c.1904C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350503.2:c.1904C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350504.2:c.1904C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_017651.5:c.1904C>T - missense variant - [Sequence Ontology: SO:0001583]


Joubert syndrome
CEREBELLOPARENCHYMAL DISORDER IV; Cerebelloparenchymal disorder 4; Cerebellar vermis agenesis; 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)
SCV001535585Invitaecriteria provided, single submitter
Uncertain significance
(Feb 2, 2020)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

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



Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]

Details of each submission

From Invitae, SCV001535585.1

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


This sequence change replaces proline with leucine at codon 635 of the AHI1 protein (p.Pro635Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs371531507, ExAC 0.002%). This variant has not been reported in the literature in individuals with AHI1-related conditions. ClinVar contains an entry for this variant (Variation ID: 355505). 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: Possibly 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: Dec 4, 2021

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