NM_020366.4(RPGRIP1):c.1107del (p.Glu370fs) AND Leber congenital amaurosis 6

Germline classification:: Pathogenic (9 submissions)
Last evaluated:: Mar 26, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000171128.18

Allele description [Variation Report for NM_020366.4(RPGRIP1):c.1107del (p.Glu370fs)]

NM_020366.4(RPGRIP1):c.1107del (p.Glu370fs)

Gene:

RPGRIP1:RPGR interacting protein 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

14q11.2

Genomic location:

Preferred name:

NM_020366.4(RPGRIP1):c.1107del (p.Glu370fs)

Other names:

p.Glu370AsnfsTer5

HGVS:

NC_000014.9:g.21312462del
NG_008933.1:g.29486del
NM_020366.4:c.1107delMANE SELECT
NP_065099.3:p.Glu370fs
NP_065099.3:p.Glu370fs
NC_000014.8:g.21780617del
NC_000014.8:g.21780621del
NM_020366.3:c.1103delA
NM_020366.3:c.1107del
NM_020366.3:c.1107del
NM_020366.3:c.1107delA
NM_020366.4:c.1107delAMANE SELECT

Protein change:

E370fs

Links:

OMIM: 605446.0004; OMIM: 605446.0009; dbSNP: rs61751266

NCBI 1000 Genomes Browser:

rs61751266

Molecular consequence:

NM_020366.4:c.1107del - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

Condition(s)

Name:: Leber congenital amaurosis 6 (LCA6)
Identifiers:: MONDO: MONDO:0013446; MedGen: C1854260; Orphanet: 65; OMIM: 613826

Recent activity

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Hipposideros beatus complex sp. lineage 2 voucher FMNH 165157 acyl-CoA oxidase 2...
Hipposideros beatus complex sp. lineage 2 voucher FMNH 165157 acyl-CoA oxidase 2 (ACOX2) gene, intron 3
gi|1840209082|gb|MT149629.1|

Nucleotide
hypothetical protein [Ruminiclostridium cellobioparum]
hypothetical protein [Ruminiclostridium cellobioparum]
gi|2811638207|ref|WP_376785780.1|

Protein
PREDICTED: Mus musculus coiled-coil domain containing 141 (Ccdc141), transcript ...
PREDICTED: Mus musculus coiled-coil domain containing 141 (Ccdc141), transcript variant X4, mRNA
gi|1907141579|ref|XM_006499913.5|

Nucleotide
coiled-coil domain-containing protein 141 isoform X1 [Mus musculus]
coiled-coil domain-containing protein 141 isoform X1 [Mus musculus]
gi|568917840|ref|XP_006499976.1|

Protein
Homologene neighbors for GEO Profiles (Select 105203824) (0)
GEO Profiles

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000025451	OMIM	no assertion criteria provided	Pathogenic (May 1, 2001)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV001133096	Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City	no assertion criteria provided	Pathogenic (Sep 26, 2019)	germline	clinical testing
SCV001426643	Centogene AG - the Rare Disease Company	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25741868, 32860008
SCV001438576	Laboratory of Genetics in Ophthalmology, Institut Imagine	no assertion criteria provided	Pathogenic	inherited	research	PubMed (1) [See all records that cite this PMID]
SCV001815997	DBGen Ocular Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jun 23, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002044747	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 7, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004806819	Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 26, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005088877	Breakthrough Genomics, Breakthrough Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 13, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	inherited	yes	1	not provided	not provided	not provided	not provided	research
unspecified	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Successful application of genome sequencing in a diagnostic setting: 1007 index cases from a clinically heterogeneous cohort.

Bertoli-Avella AM, Beetz C, Ameziane N, Rocha ME, Guatibonza P, Pereira C, Calvo M, Herrera-Ordonez N, Segura-Castel M, Diego-Alvarez D, Zawada M, Kandaswamy KK, Werber M, Paknia O, Zielske S, Ugrinovski D, Warnack G, Kampe K, Iurașcu MI, Cozma C, Vogel F, Alhashem A, et al.

Eur J Hum Genet. 2021 Jan;29(1):141-153. doi: 10.1038/s41431-020-00713-9. Epub 2020 Aug 28.

PubMed [citation]

PMID:: 32860008
PMCID:: PMC7852664

Null RPGRIP1 alleles in patients with Leber congenital amaurosis.

Dryja TP, Adams SM, Grimsby JL, McGee TL, Hong DH, Li T, Andréasson S, Berson EL.

Am J Hum Genet. 2001 May;68(5):1295-8. Epub 2001 Mar 29.

PubMed [citation]

PMID:: 11283794
PMCID:: PMC1226111

See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000025451.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City, SCV001133096.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Centogene AG - the Rare Disease Company, SCV001426643.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Laboratory of Genetics in Ophthalmology, Institut Imagine, SCV001438576.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	research	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	inherited	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

From DBGen Ocular Genomics, SCV001815997.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	unspecified	1	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

From Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital, SCV001984513.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Genome-Nilou Lab, SCV002044747.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, SCV004806819.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Breakthrough Genomics, Breakthrough Genomics, SCV005088877.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This variant has been observed in homozygous state in multiple individuals with a clinical diagnosis of Leber congenital amaurosis [PMID: 30202406, 20079931, 24997176] and it was previously reported as recurrent variant (represented as c.1007delA (p.Glu370Asnfs*5) in the article [PMID: 24997176].

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Flagged submissions

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001984513	Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital	flagged submission Reason: This record appears to be redundant with a more recent record from the same submitter. Notes: SCV001984513 appears to be redundant with SCV002818118. (ACMG Guidelines, 2015)	Pathogenic (Apr 7, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001984513

Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital

flagged submission

Reason: This record appears to be redundant with a more recent record from the same submitter.

Notes: SCV001984513 appears to be redundant with SCV002818118.

(ACMG Guidelines, 2015)

Pathogenic
(Apr 7, 2020)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Last Updated: Sep 29, 2024

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