This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 896 of the AHI1 protein (p.His896Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with Joubert syndrome or non-syndromic retinal dystrophy (PMID: 16155189, 28442542; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 217532). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt AHI1 protein function. For these reasons, this variant has been classified as Pathogenic.
ClinVar Genomic variation as it relates to human health
Help
- Interpretation:
-
Pathogenic
- Review status:
- criteria provided, multiple submitters, no conflicts
- Submissions:
- 3
- First in ClinVar:
- Nov 9, 2015
- Most recent Submission:
- Feb 7, 2023
- Last evaluated:
- Jul 5, 2022
- Accession:
- VCV000217532.19
- Variation ID:
- 217532
- Description:
- single nucleotide variant
Help
NM_001134831.2(AHI1):c.2687A>G (p.His896Arg)
- Allele ID
- 214231
- Variant type
- single nucleotide variant
- Variant length
- 1 bp
- Cytogenetic location
- 6q23.3
- Genomic location
- 6: 135427244 (GRCh38) GRCh38 UCSC
- 6: 135748382 (GRCh37) GRCh37 UCSC
- HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001134831.2:c.2687A>G MANE Select NP_001128303.1:p.His896Arg missense NM_001134830.2:c.2687A>G NP_001128302.1:p.His896Arg missense NM_001134832.2:c.2687A>G NP_001128304.1:p.His896Arg missense NM_001350503.2:c.2687A>G NP_001337432.1:p.His896Arg missense NM_001350504.2:c.2687A>G NP_001337433.1:p.His896Arg missense NM_017651.5:c.2687A>G NP_060121.3:p.His896Arg missense NC_000006.12:g.135427244T>C NC_000006.11:g.135748382T>C NG_008643.2:g.75522A>G Q8N157:p.His896Arg - Protein change
- H896R
- Other names
- -
- Canonical SPDI
- NC_000006.12:135427243:T:C
- Functional consequence
- -
- Global minor allele frequency (GMAF)
- -
- Allele frequency
- Trans-Omics for Precision Medicine (TOPMed) 0.00002
- The Genome Aggregation Database (gnomAD) 0.00001
- Trans-Omics for Precision Medicine (TOPMed) 0.00001
- Links
- ClinGen: CA279374
- UniProtKB: Q8N157#VAR_076822
- dbSNP: rs863225135
- VarSome
Help
Aggregate interpretations per condition
| Interpreted condition | Interpretation | Number of submissions | Review status | Last evaluated | Variation/condition record |
|---|---|---|---|---|---|
| Pathogenic | 1 | criteria provided, single submitter | Feb 23, 2015 | RCV000201566.1 | |
| Pathogenic | 1 | criteria provided, single submitter | Jul 1, 2017 | RCV001091216.9 | |
| Pathogenic | 1 | criteria provided, single submitter | Jul 5, 2022 | RCV001240194.6 |
Submitted interpretations and evidence
Help| Interpretation (Last evaluated) |
Review status (Assertion criteria) |
Condition (Inheritance) |
Submitter | More information | |
|---|---|---|---|---|---|
|
Pathogenic
(Feb 23, 2015)
|
criteria provided, single submitter
Method: research
|
Joubert syndrome 3
Affected status: yes
Allele origin:
unknown
|
UW Hindbrain Malformation Research Program,University of Washington
Additional submitter:
University of Washington Center for Mendelian Genomics, University of Washington
Accession: SCV000256257.1
First in ClinVar: Nov 09, 2015 Last updated: Nov 09, 2015 |
|
|
|
Pathogenic
(Jul 01, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV001247114.13
First in ClinVar: May 12, 2020 Last updated: Jan 21, 2023 |
Number of individuals with the variant: 1
|
|
|
Pathogenic
(Jul 05, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Joubert syndrome
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV001413119.4
First in ClinVar: Jul 16, 2020 Last updated: Feb 07, 2023 |
Comment:
This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 896 of the AHI1 protein (p.His896Arg). … (more)
This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 896 of the AHI1 protein (p.His896Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with Joubert syndrome or non-syndromic retinal dystrophy (PMID: 16155189, 28442542; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 217532). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt AHI1 protein function. For these reasons, this variant has been classified as Pathogenic. (less)
|
Functional evidence
Help| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Missense mutations in the WD40 domain of AHI1 cause non-syndromic retinitis pigmentosa. | Nguyen TT | Journal of medical genetics | 2017 | PMID: 28442542 |
| Joubert syndrome: a model for untangling recessive disorders with extreme genetic heterogeneity. | Bachmann-Gagescu R | Journal of medical genetics | 2015 | PMID: 26092869 |
| AHI1 mutations cause both retinal dystrophy and renal cystic disease in Joubert syndrome. | Parisi MA | Journal of medical genetics | 2006 | PMID: 16155189 |
Text-mined citations for rs863225135...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Feb 13, 2023