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NM_152443.3(RDH12):c.295C>A (p.Leu99Ile)

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Interpretation:
Pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
11 (Most recent: Aug 20, 2021)
Last evaluated:
Apr 27, 2021
Accession:
VCV000002055.12
Variation ID:
2055
Description:
single nucleotide variant
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NM_152443.3(RDH12):c.295C>A (p.Leu99Ile)

Allele ID
17094
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
14q24.1
Genomic location
14: 67725206 (GRCh38) GRCh38 UCSC
14: 68191923 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
Q96NR8:p.Leu99Ile
NC_000014.8:g.68191923C>A
NC_000014.9:g.67725206C>A
... more HGVS
Protein change
L99I
Other names
-
Canonical SPDI
NC_000014.9:67725205:C:A
Functional consequence
-
Global minor allele frequency (GMAF)
0.00040 (A)

Allele frequency
Trans-Omics for Precision Medicine (TOPMed) 0.00002
The Genome Aggregation Database (gnomAD), exomes 0.00006
The Genome Aggregation Database (gnomAD) 0.00003
Exome Aggregation Consortium (ExAC) 0.00007
1000 Genomes Project 0.00040
Links
ClinGen: CA252088
UniProtKB: Q96NR8#VAR_020860
OMIM: 608830.0010
dbSNP: rs28940315
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 5 criteria provided, multiple submitters, no conflicts Apr 8, 2021 RCV000002136.10
Pathogenic 2 criteria provided, multiple submitters, no conflicts Apr 27, 2021 RCV000594844.3
Pathogenic 1 criteria provided, single submitter Aug 8, 2019 RCV001075855.1
Pathogenic 2 no assertion criteria provided Aug 1, 2019 RCV000993758.2
Pathogenic 1 no assertion criteria provided Sep 16, 2020 RCV001277202.1
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
RDH12 - - GRCh38
GRCh37
185 294

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Aug 08, 2019)
criteria provided, single submitter
Method: clinical testing
Retinal dystrophy
Allele origin: germline
Blueprint Genetics
Accession: SCV001241494.1
Submitted: (Oct 15, 2019)
Comment:
My Retina Tracker patient
Evidence details
Pathogenic
(Sep 30, 2020)
criteria provided, single submitter
Method: clinical testing
Leber congenital amaurosis 13
Allele origin: germline
Invitae
Accession: SCV000767478.5
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (6)
Comment:
This sequence change replaces leucine with isoleucine at codon 99 of the RDH12 protein (p.Leu99Ile). The leucine residue is highly conserved and there is a … (more)
Pathogenic
(Apr 27, 2021)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV001802381.1
Submitted: (Aug 20, 2021)
Evidence details
Comment:
Published functional studies demonstrate a damaging effect: reduced ability to convert all-trans retinal to all-trans retinol in the presence of NADPH, with roughly 10% catalytic … (more)
Pathogenic
(Oct 21, 2016)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics
Accession: SCV000701365.2
Submitted: (Sep 19, 2018)
Evidence details
Publications
PubMed (6)
Other databases
http://www.egl-eurofins.com/emvc…
Pathogenic
(May 28, 2019)
criteria provided, single submitter
Method: clinical testing
Leber congenital amaurosis 13
Allele origin: unknown
Mendelics
Accession: SCV001139477.1
Submitted: (Oct 22, 2019)
Evidence details
Pathogenic
(Apr 08, 2021)
criteria provided, single submitter
Method: research
Leber congenital amaurosis 13
Allele origin: germline
Ocular Genomics Institute, Massachusetts Eye and Ear
Accession: SCV001573615.1
Submitted: (Apr 26, 2021)
Evidence details
Publications
PubMed (10)
Comment:
The RDH12 c.295C>A variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we … (more)
Pathogenic
(Oct 01, 2004)
no assertion criteria provided
Method: literature only
LEBER CONGENITAL AMAUROSIS 13
Allele origin: germline
OMIM
Accession: SCV000022294.2
Submitted: (Dec 30, 2010)
Evidence details
Publications
PubMed (1)
Pathogenic
(Aug 01, 2019)
no assertion criteria provided
Method: clinical testing
Retinitis pigmentosa
Allele origin: germline
Ocular Genomics Institute, Massachusetts Eye and Ear
Accession: SCV001146952.1
Submitted: (Aug 30, 2019)
Evidence details
Pathogenic
(Jun 23, 2019)
no assertion criteria provided
Method: research
Retinitis pigmentosa
Allele origin: inherited
Sharon lab,Hadassah-Hebrew University Medical Center
Accession: SCV001161223.1
Submitted: (Jun 25, 2019)
Evidence details
Pathogenic
(-)
no assertion criteria provided
Method: research
Leber congenital amaurosis 13
Allele origin: inherited
Laboratory of Genetics in Ophthalmology,Institut Imagine
Accession: SCV001432271.1
Submitted: (May 25, 2020)
Evidence details
Publications
PubMed (1)
Pathogenic
(Sep 16, 2020)
no assertion criteria provided
Method: clinical testing
Leber congenital amaurosis
Allele origin: germline
Natera, Inc.
Accession: SCV001464101.1
Submitted: (Dec 28, 2020)
Evidence details

Functional evidence

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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

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Title Author Journal Year Link
Expanding the phenotypic spectrum in RDH12-associated retinal disease. Scott HA Cold Spring Harbor molecular case studies 2020 PMID: 32014858
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532
Improving the management of Inherited Retinal Dystrophies by targeted sequencing of a population-specific gene panel. Bravo-Gil N Scientific reports 2016 PMID: 27032803
NGS-based Molecular diagnosis of 105 eyeGENE(®) probands with Retinitis Pigmentosa. Ge Z Scientific reports 2015 PMID: 26667666
Whole Exome Sequencing Reveals Mutations in Known Retinal Disease Genes in 33 out of 68 Israeli Families with Inherited Retinopathies. Beryozkin A Scientific reports 2015 PMID: 26306921
Identification of mutations causing inherited retinal degenerations in the israeli and palestinian populations using homozygosity mapping. Beryozkin A Investigative ophthalmology & visual science 2014 PMID: 24474277
Exome sequencing identifies RDH12 compound heterozygous mutations in a family with severe retinitis pigmentosa. Chacon-Camacho OF Gene 2013 PMID: 23900199
RDH12 retinopathy: novel mutations and phenotypic description. Mackay DS Molecular vision 2011 PMID: 22065924
Retinal degeneration associated with RDH12 mutations results from decreased 11-cis retinal synthesis due to disruption of the visual cycle. Thompson DA Human molecular genetics 2005 PMID: 16269441
Retinal dehydrogenase 12 (RDH12) mutations in leber congenital amaurosis. Perrault I American journal of human genetics 2004 PMID: 15322982
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=RDH12 - - - -

Text-mined citations for rs28940315...

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These 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 Sep 24, 2021