ClinVar Genomic variation as it relates to human health
NM_001012720.2(RGR):c.196A>C (p.Ser66Arg)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Likely pathogenic(1); Uncertain significance(5)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001012720.2(RGR):c.196A>C (p.Ser66Arg)
Variation ID: 9181 Accession: VCV000009181.16
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 10q23.1 10: 84247707 (GRCh38) [ NCBI UCSC ] 10: 86007463 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 4, 2013 Feb 14, 2024 Nov 17, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001012720.2:c.196A>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001012738.1:p.Ser66Arg missense NM_001012722.2:c.196A>C NP_001012740.1:p.Ser66Arg missense NM_002921.4:c.196A>C NP_002912.2:p.Ser66Arg missense NC_000010.11:g.84247707A>C NC_000010.10:g.86007463A>C NG_009106.1:g.7655A>C - Protein change
- S66R
- Other names
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- Canonical SPDI
- NC_000010.11:84247706:A:C
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
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The frequency of the allele represented by this VCV record.
Exome Aggregation Consortium (ExAC) 0.00002
The Genome Aggregation Database (gnomAD) 0.00002
The Genome Aggregation Database (gnomAD), exomes 0.00003
Trans-Omics for Precision Medicine (TOPMed) 0.00003
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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RGR | - | - |
GRCh38 GRCh37 |
280 | 327 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
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Jan 20, 2022 | RCV000009759.8 | |
Uncertain significance (3) |
criteria provided, multiple submitters, no conflicts
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Nov 17, 2023 | RCV000175649.12 | |
Uncertain significance (1) |
criteria provided, single submitter
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Jan 1, 2017 | RCV000626831.2 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
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The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
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The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
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This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Uncertain significance
(Jun 25, 2015)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000227178.5
First in ClinVar: Jun 29, 2015 Last updated: Dec 06, 2016 |
Number of individuals with the variant: 3
Sex: mixed
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Likely pathogenic
(Jan 20, 2022)
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criteria provided, single submitter
Method: clinical testing
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Retinitis pigmentosa 44
Affected status: yes
Allele origin:
unknown
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Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV002072559.1
First in ClinVar: Feb 03, 2022 Last updated: Feb 03, 2022 |
Comment:
This variant was identified as homozygous. Another variant (NM_033100.4:c.2522_2528del) was found in the same patient. Criteria applied: PS4_MOD, PM3, PM2_SUP, PP3
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Uncertain significance
(Sep 18, 2020)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV001986231.2
First in ClinVar: Nov 06, 2021 Last updated: Mar 04, 2023 |
Comment:
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27623334, … (more)
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27623334, 10581022, 21067480, 30337596) (less)
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Uncertain significance
(Nov 17, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001202194.5
First in ClinVar: Apr 15, 2020 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 66 of the RGR protein (p.Ser66Arg). … (more)
This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 66 of the RGR protein (p.Ser66Arg). This variant is present in population databases (rs104894187, gnomAD 0.007%). This missense change has been observed in individual(s) with RGR-related conditions (PMID: 27623334, 30337596, 32531858, 34229535). ClinVar contains an entry for this variant (Variation ID: 9181). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. (less)
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Uncertain significance
(Jan 01, 2017)
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criteria provided, single submitter
Method: clinical testing
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Cone-rod dystrophy
Affected status: yes
Allele origin:
unknown
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Centre for Mendelian Genomics, University Medical Centre Ljubljana
Accession: SCV000747534.1
First in ClinVar: May 12, 2018 Last updated: May 12, 2018 |
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Uncertain significance
(Feb 21, 2019)
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criteria provided, single submitter
Method: clinical testing
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Retinitis pigmentosa 44
Affected status: yes
Allele origin:
unknown
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Centre for Mendelian Genomics, University Medical Centre Ljubljana
Accession: SCV001370118.2
First in ClinVar: Jul 04, 2020 Last updated: Dec 12, 2020 |
Comment:
This variant was classified as: Uncertain significance. The following ACMG criteria were applied in classifying this variant: PM2,PP3,PP5.
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Pathogenic
(Dec 01, 1999)
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no assertion criteria provided
Method: literature only
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RETINITIS PIGMENTOSA 44
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000029980.1
First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013 |
Comment on evidence:
In 5 sibs with retinitis pigmentosa (RP44; 613769), Morimura et al. (1999) identified a homozygous A-to-C transversion in the RGR gene resulting in a ser66-to-arg … (more)
In 5 sibs with retinitis pigmentosa (RP44; 613769), Morimura et al. (1999) identified a homozygous A-to-C transversion in the RGR gene resulting in a ser66-to-arg (S66R) amino acid substitution. The parents denied consanguinity. Haplotype analyses suggested that the mutant allele in the parents had a common ancestral origin. The patients in this family, aged 35 to 44, with the ser66-to-arg mutation had visual acuity of 20/200 or worse, severely constricted visual fields, attenuated retinal vessels, diffuse depigmentation of the retinal pigment epithelium, and intraretinal pigment deposits in the periphery. The depigmented patches involved the central macula in those sibs with severely decreased acuity. Full-field electroretinograms reflected widespread loss of photoreceptor function. (less)
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Germline Functional Evidence
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 germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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A rare case of RGR/CDHR1 haplotype identified in Bulgarian patient with cone-rod dystrophy. | Mermeklieva E | Ophthalmic genetics | 2021 | PMID: 34229535 |
Genetic architecture of inherited retinal degeneration in Germany: A large cohort study from a single diagnostic center over a 9-year period. | Weisschuh N | Human mutation | 2020 | PMID: 32531858 |
A new approach based on targeted pooled DNA sequencing identifies novel mutations in patients with Inherited Retinal Dystrophies. | Ezquerra-Inchausti M | Scientific reports | 2018 | PMID: 30337596 |
Reevaluation of the Retinal Dystrophy Due to Recessive Alleles of RGR With the Discovery of a Cis-Acting Mutation in CDHR1. | Arno G | Investigative ophthalmology & visual science | 2016 | PMID: 27623334 |
Mutations in RGR, encoding a light-sensitive opsin homologue, in patients with retinitis pigmentosa. | Morimura H | Nature genetics | 1999 | PMID: 10581022 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=RGR | - | - | - | - |
Text-mined citations for rs104894187 ...
HelpRecord last updated Feb 20, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.