ClinVar Genomic variation as it relates to human health
NM_006269.2(RP1):c.5797C>T (p.Arg1933Ter)
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.
Pathogenic(3); Likely pathogenic(1); Uncertain significance(1); Benign(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_006269.2(RP1):c.5797C>T (p.Arg1933Ter)
Variation ID: 143136 Accession: VCV000143136.19
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 8q12.1 8: 54629679 (GRCh38) [ NCBI UCSC ] 8: 55542239 (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 Aug 10, 2014 Mar 10, 2024 Oct 1, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_006269.2:c.5797C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_006260.1:p.Arg1933Ter nonsense NC_000008.11:g.54629679C>T NC_000008.10:g.55542239C>T NG_009840.2:g.18613C>T - Protein change
- R1933*
- Other names
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- Canonical SPDI
- NC_000008.11:54629678:C:T
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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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0.00040 (T)
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Allele frequency
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The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD), exomes 0.00018
1000 Genomes Project 30x 0.00031
1000 Genomes Project 0.00040
The Genome Aggregation Database (gnomAD) 0.00008
Trans-Omics for Precision Medicine (TOPMed) 0.00009
Exome Aggregation Consortium (ExAC) 0.00013
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
Help
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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LOC126860392 | - | - | - | GRCh38 | - | 247 |
RP1 | - | - |
GRCh38 GRCh37 |
1263 | 1525 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
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
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
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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Benign (2) |
criteria provided, single submitter
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May 4, 2017 | RCV000132661.5 | |
Pathogenic/Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Aug 10, 2023 | RCV001035254.7 | |
Uncertain significance (1) |
criteria provided, single submitter
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Dec 13, 2018 | RCV000825444.4 | |
Pathogenic (1) |
criteria provided, single submitter
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May 22, 2022 | RCV002250573.1 | |
Pathogenic (1) |
criteria provided, single submitter
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Oct 1, 2023 | RCV003888563.1 |
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
Help
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
Help
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
(Dec 13, 2018)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: not provided
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000966744.1
First in ClinVar: Aug 26, 2019 Last updated: Aug 26, 2019 |
Comment:
Variant classified as Uncertain Significance - Favor Pathogenic. The p.Arg1933X variant in RP1 has been reported in the heterozygous state in 4 individuals with occult … (more)
Variant classified as Uncertain Significance - Favor Pathogenic. The p.Arg1933X variant in RP1 has been reported in the heterozygous state in 4 individuals with occult macular dystrophy, in 1 homozygous individual with retinitis pigmentosa, and in 4 individuals with hereditary ciliary retinopathy in compound heterozygo sity with an Alu insertion (c.4052_4053ins328) (Fujinami 2016, Li 2018, Maeda 20 18, Nikopoulos 2018). It has also been identified in 0.2% (41/19950) of East Asi an chromosomes by gnomAD (http://gnomad.broadinstitute.org).This nonsense varian t leads to a premature termination codon at position 1933. This alteration occur s within the last exon and is, therefore, likely to escape nonsense mediated dec ay (NMD) and result in a truncated protein. In summary, while there is some susp icion for a pathogenic role, the clinical significance of the p.Arg1933X variant is uncertain. ACMG/AMP Criteria applied: PM4, PM3. (less)
Number of individuals with the variant: 1
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Benign
(May 04, 2017)
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criteria provided, single submitter
Method: clinical testing
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Retinitis pigmentosa
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001325378.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. (less)
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Likely pathogenic
(Nov 30, 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: SCV001830662.1
First in ClinVar: Sep 08, 2021 Last updated: Sep 08, 2021 |
Comment:
Nonsense variant in the C-terminus predicted to result in protein truncation, as the last 224 amino acids are lost, and other loss-of-function variants have been … (more)
Nonsense variant in the C-terminus predicted to result in protein truncation, as the last 224 amino acids are lost, and other loss-of-function variants have been reported downstream in the Human Gene Mutation Database (Stenson et al., 2014); This variant is associated with the following publications: (PMID: 33090715, 31980526, 15183808, 31054281, 30913292, 11857735, 16085945, 29785639, 31253780, 12048676, 12901510, 22321012, 18450588, 15994872, 11694261, 11317367, 27623337, 29425069) (less)
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Pathogenic
(May 22, 2022)
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criteria provided, single submitter
Method: clinical testing
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Retinitis pigmentosa 1
Affected status: yes
Allele origin:
germline
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3billion
Accession: SCV002521245.1
First in ClinVar: Jun 03, 2022 Last updated: Jun 03, 2022 |
Comment:
The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.017%). Stop-gained (nonsense): predicted to result in a … (more)
The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.017%). Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through protein truncation. Multiple pathogenic variants are reported in the predicted truncated region. The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000143136 / 3billion dataset). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. (less)
Clinical Features:
Blindness (present)
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Pathogenic
(Oct 01, 2023)
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criteria provided, single submitter
Method: research
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Retinal dystrophy
Affected status: yes
Allele origin:
germline
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Dept Of Ophthalmology, Nagoya University
Accession: SCV004706761.1
First in ClinVar: Mar 10, 2024 Last updated: Mar 10, 2024 |
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Pathogenic
(Aug 10, 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: SCV001198577.5
First in ClinVar: Apr 15, 2020 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminus of the RP1 protein. Many variants that disrupt this region … (more)
For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminus of the RP1 protein. Many variants that disrupt this region have been reported in individuals with either autosomal dominant or autosomal recessive retinitis pigmentosa (PMID: 11527933, 19933189, 29425069, 30027431, 33681214). Therefore, variants that disrupt this region are expected to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 143136). This premature translational stop signal has been observed to be homozygous or hemizygous in an individual who did not have the expected clinical features for that genetic result (PMID: 31253780). This premature translational stop signal has been observed in individual(s) with autosomal recessive retinitis pigmentosa (PMID: 29425069, 30913292, 31253780). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs118031911, gnomAD 0.2%). This sequence change creates a premature translational stop signal (p.Arg1933*) in the RP1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 224 amino acid(s) of the RP1 protein. (less)
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probable-pathogenic
(-)
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no assertion criteria provided
Method: not provided
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Retinitis pigmentosa
Affected status: not provided
Allele origin:
not provided
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Department of Ophthalmology and Visual Sciences Kyoto University
Accession: SCV000172612.1
First in ClinVar: Aug 10, 2014 Last updated: Aug 10, 2014 |
Comment:
Converted during submission to Likely pathogenic.
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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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Dominant RP in the Middle While Recessive in Both the N- and C-Terminals Due to RP1 Truncations: Confirmation, Refinement, and Questions. | Wang J | Frontiers in cell and developmental biology | 2021 | PMID: 33681214 |
A frequent variant in the Japanese population determines quasi-Mendelian inheritance of rare retinal ciliopathy. | Nikopoulos K | Nature communications | 2019 | PMID: 31253780 |
Macular Dystrophy and Cone-Rod Dystrophy Caused by Mutations in the RP1 Gene: Extending the RP1 Disease Spectrum. | Verbakel SK | Investigative ophthalmology & visual science | 2019 | PMID: 30913292 |
Clinical and genetic findings of a Japanese patient with RP1-related autosomal recessive retinitis pigmentosa. | Kurata K | Documenta ophthalmologica. Advances in ophthalmology | 2018 | PMID: 30027431 |
Development of a molecular diagnostic test for Retinitis Pigmentosa in the Japanese population. | Maeda A | Japanese journal of ophthalmology | 2018 | PMID: 29785639 |
Targeted Next-Generation Sequencing Reveals Novel RP1 Mutations in Autosomal Recessive Retinitis Pigmentosa. | Li S | Genetic testing and molecular biomarkers | 2018 | PMID: 29425069 |
Novel RP1L1 Variants and Genotype-Photoreceptor Microstructural Phenotype Associations in Cohort of Japanese Patients With Occult Macular Dystrophy. | Fujinami K | Investigative ophthalmology & visual science | 2016 | PMID: 27623337 |
Compound heterozygosity of two novel truncation mutations in RP1 causing autosomal recessive retinitis pigmentosa. | Chen LJ | Investigative ophthalmology & visual science | 2010 | PMID: 19933189 |
Molecular genetics of autosomal dominant retinitis pigmentosa (ADRP): a comprehensive study of 43 Italian families. | Ziviello C | Journal of medical genetics | 2005 | PMID: 15994872 |
Novel 2336-2337delCT mutation in RP1 gene in a Japanese family with autosomal dominant retinitis pigmentosa. | Kawamura M | American journal of ophthalmology | 2004 | PMID: 15183808 |
Molecular diagnostics for retinitis pigmentosa. | Yeung KY | Clinica chimica acta; international journal of clinical chemistry | 2001 | PMID: 11694261 |
Clinical features and mutations in patients with dominant retinitis pigmentosa-1 (RP1). | Berson EL | Investigative ophthalmology & visual science | 2001 | PMID: 11527933 |
RP1 in Chinese: Eight novel variants and evidence that truncation of the extreme C-terminal does not cause retinitis pigmentosa. | Baum L | Human mutation | 2001 | PMID: 11317367 |
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Text-mined citations for rs118031911 ...
HelpRecord last updated Mar 17, 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.