ClinVar Genomic variation as it relates to human health
NM_020366.4(RPGRIP1):c.1107del (p.Glu370fs)
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_020366.4(RPGRIP1):c.1107del (p.Glu370fs)
Variation ID: 99809 Accession: VCV000099809.21
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 14q11.2 14: 21312458 (GRCh38) [ NCBI UCSC ] 14: 21780617 (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 Feb 20, 2014 Apr 6, 2024 Mar 26, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_020366.4:c.1107del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_065099.3:p.Glu370fs frameshift NM_020366.4:c.1107delA MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
frameshift NM_020366.3:c.1103delA NM_020366.3:c.1107delA NC_000014.9:g.21312462del NC_000014.8:g.21780621del NG_008933.1:g.29486del - Protein change
- E370fs
- Other names
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- Canonical SPDI
- NC_000014.9:21312457:AAAAA:AAAA
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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.
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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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RPGRIP1 | - | - |
GRCh38 GRCh37 |
1012 | 1061 |
Conditions - Germline
Condition
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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
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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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Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Dec 17, 2022 | RCV000086238.6 | |
Pathogenic (8) |
criteria provided, multiple submitters, no conflicts
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Mar 26, 2024 | RCV000171128.15 | |
Pathogenic (1) |
no assertion criteria provided
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Dec 13, 2017 | RCV000786015.1 | |
Pathogenic (1) |
criteria provided, single submitter
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Feb 8, 2023 | RCV001047199.5 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Jan 3, 2022 | RCV001800395.3 |
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
Help
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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Pathogenic
(Jun 23, 2021)
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criteria provided, single submitter
Method: clinical testing
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Leber congenital amaurosis 6
Affected status: yes
Allele origin:
germline
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DBGen Ocular Genomics
Accession: SCV001815997.1
First in ClinVar: Sep 08, 2021 Last updated: Sep 08, 2021 |
Number of individuals with the variant: 1
Sex: female
Ethnicity/Population group: unspecified
Geographic origin: Middle East
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Pathogenic
(Feb 03, 2021)
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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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Revvity Omics, Revvity
Accession: SCV002019890.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(Mar 26, 2024)
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criteria provided, single submitter
Method: clinical testing
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Leber congenital amaurosis 6
Affected status: unknown
Allele origin:
germline
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Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center
Accession: SCV004806819.1
First in ClinVar: Apr 06, 2024 Last updated: Apr 06, 2024 |
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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Leber congenital amaurosis 6
Affected status: yes
Allele origin:
germline
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Centogene AG - the Rare Disease Company
Accession: SCV001426643.1
First in ClinVar: Aug 09, 2020 Last updated: Aug 09, 2020 |
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Pathogenic
(Dec 17, 2022)
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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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Al Jalila Children's Genomics Center, Al Jalila Childrens Speciality Hospital
Accession: SCV002818118.1
First in ClinVar: Jan 07, 2023 Last updated: Jan 07, 2023 |
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Pathogenic
(Feb 08, 2023)
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criteria provided, single submitter
Method: clinical testing
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Leber congenital amaurosis 6
Cone-rod dystrophy 13
Explanation for multiple conditions: Uncertain.
The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001211139.5
First in ClinVar: Apr 15, 2020 Last updated: Feb 28, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Glu370Asnfs*5) in the RPGRIP1 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Glu370Asnfs*5) in the RPGRIP1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RPGRIP1 are known to be pathogenic (PMID: 11528500, 23105016). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with Leber congenital amaurosis (PMID: 11283794, 20079931, 24997176, 30202406). This variant is also known as Lys342(1-bp del). ClinVar contains an entry for this variant (Variation ID: 99809). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Nov 07, 2021)
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criteria provided, single submitter
Method: clinical testing
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Leber congenital amaurosis 6
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV002044747.1
First in ClinVar: Jan 03, 2022 Last updated: Jan 03, 2022 |
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Pathogenic
(Nov 07, 2021)
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criteria provided, single submitter
Method: clinical testing
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Cone-rod dystrophy 13
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV002044758.1
First in ClinVar: Jan 03, 2022 Last updated: Jan 03, 2022 |
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Pathogenic
(Jan 03, 2022)
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criteria provided, single submitter
Method: clinical testing
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Cone-rod dystrophy 13
Affected status: yes
Allele origin:
germline
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3billion
Accession: SCV002058264.1
First in ClinVar: Jan 15, 2022 Last updated: Jan 15, 2022 |
Comment:
Frameshift: predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported … (more)
Frameshift: predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant (PVS1_VS). The variant has been reported at least twice as pathogenic/likely pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000099809, PMID:11283794). It is not observed in the gnomAD v2.1.1 dataset (PM2_M).. Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. (less)
Clinical Features:
Rod-cone dystrophy (present)
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Pathogenic
(May 01, 2001)
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no assertion criteria provided
Method: literature only
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LEBER CONGENITAL AMAUROSIS 6
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000025451.2
First in ClinVar: Apr 04, 2013 Last updated: May 23, 2015 |
Comment on evidence:
In a patient with Leber congenital amaurosis-6 (LCA6; 613826), Dryja et al. (2001) identified homozygosity for a frameshift mutation in the RPGRIP1 gene. The mutation … (more)
In a patient with Leber congenital amaurosis-6 (LCA6; 613826), Dryja et al. (2001) identified homozygosity for a frameshift mutation in the RPGRIP1 gene. The mutation consisted of a 1-bp deletion (A) at codon lys342. (less)
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Pathogenic
(Dec 13, 2017)
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no assertion criteria provided
Method: research
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Leber congenital amaurosis
Affected status: yes
Allele origin:
inherited
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Molecular Genetics Laboratory, Institute for Ophthalmic Research
Accession: SCV000924655.1
First in ClinVar: Jun 28, 2019 Last updated: Jun 28, 2019 |
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Pathogenic
(Sep 26, 2019)
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no assertion criteria provided
Method: clinical testing
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Leber congenital amaurosis 6
Affected status: yes
Allele origin:
germline
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Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City
Accession: SCV001133096.1
First in ClinVar: Jan 04, 2020 Last updated: Jan 04, 2020 |
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Pathogenic
(-)
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no assertion criteria provided
Method: research
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Leber congenital amaurosis 6
Affected status: yes
Allele origin:
inherited
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Laboratory of Genetics in Ophthalmology, Institut Imagine
Accession: SCV001438576.1
First in ClinVar: Oct 23, 2020 Last updated: Oct 23, 2020 |
Number of individuals with the variant: 1
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not provided
(-)
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no classification provided
Method: not provided
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not provided
Affected status: not provided
Allele origin:
not provided
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Retina International
Accession: SCV000118384.1
First in ClinVar: Feb 20, 2014 Last updated: Feb 20, 2014
Comment:
http://phencode.bx.psu.edu/cgi-bin/phencode/phencode?build=hg19&id=RISN_RPGRIP:c.1103delA
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Pathogenic
(Apr 07, 2020)
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Flagged submission
flagged submission
Method: clinical testing
Reason: This record appears to be redundant with a more recent record from the same submitter.
Notes: SCV001984513 appears to be redundant with SCV002818118.
(less)
Notes: SCV001984513 appears to
(...more)
Source: NCBI
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Leber congenital amaurosis 6
Affected status: yes
Allele origin:
germline
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Al Jalila Children's Genomics Center, Al Jalila Childrens Speciality Hospital
Accession: SCV001984513.1
First in ClinVar: Oct 30, 2021 Last updated: Oct 30, 2021
Comment:
The p.Glu370fs variant in RPGRIP1 has been previously reported in at least one individual with congenital leber amaurosis (PMIDs: 11283794) but was absent from large … (more)
The p.Glu370fs variant in RPGRIP1 has been previously reported in at least one individual with congenital leber amaurosis (PMIDs: 11283794) but was absent from large population studies such as the Genome Aggregation Database (gnomAD) and the Greater Middle East (GME) Variome Database. This frameshift variant affecting the only known RPGRIP1 transcript is predicted to alter the protein's amino acid sequence beginning at position 370 and lead to a premature termination codon 5 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. In summary this variant meets our criteria for pathogenicity. (less)
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Flagged submissions do not contribute to the aggregate classification or review status for the variant. Learn more |
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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Successful application of genome sequencing in a diagnostic setting: 1007 index cases from a clinically heterogeneous cohort. | Bertoli-Avella AM | European journal of human genetics : EJHG | 2021 | PMID: 32860008 |
Applying filtration steps to interpret the results of whole-exome sequencing in a consanguineous population to achieve a high detection rate. | Alfares AA | International journal of health sciences | 2018 | PMID: 30202406 |
Genetic analysis of strictly defined Leber congenital amaurosis with (and without) neurodevelopmental delay. | Khan AO | The British journal of ophthalmology | 2014 | PMID: 24997176 |
Autozygome-guided exome sequencing in retinal dystrophy patients reveals pathogenetic mutations and novel candidate disease genes. | Abu-Safieh L | Genome research | 2013 | PMID: 23105016 |
Visual acuity in patients with Leber's congenital amaurosis and early childhood-onset retinitis pigmentosa. | Walia S | Ophthalmology | 2010 | PMID: 20079931 |
Complete exon-intron structure of the RPGR-interacting protein (RPGRIP1) gene allows the identification of mutations underlying Leber congenital amaurosis. | Gerber S | European journal of human genetics : EJHG | 2001 | PMID: 11528500 |
Null RPGRIP1 alleles in patients with Leber congenital amaurosis. | Dryja TP | American journal of human genetics | 2001 | PMID: 11283794 |
Text-mined citations for rs61751266 ...
HelpRecord last updated May 08, 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.