NM_201253.3(CRB1):c.3331G>T (p.Glu1111Ter) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 23, 2021
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV002514530.3

Allele description [Variation Report for NM_201253.3(CRB1):c.3331G>T (p.Glu1111Ter)]

NM_201253.3(CRB1):c.3331G>T (p.Glu1111Ter)

Gene:

CRB1:crumbs cell polarity complex component 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q31.3

Genomic location:

Preferred name:

NM_201253.3(CRB1):c.3331G>T (p.Glu1111Ter)

HGVS:

NC_000001.11:g.197435194G>T
NG_008483.2:g.238733G>T
NM_001193640.2:c.2995G>T
NM_001257965.2:c.3259G>T
NM_001257966.2:c.2129-406G>T
NM_201253.3:c.3331G>TMANE SELECT
NP_001180569.1:p.Glu999Ter
NP_001244894.1:p.Glu1087Ter
NP_957705.1:p.Glu1111Ter
NC_000001.10:g.197404324G>T
NM_201253.2:c.3331G>T
NR_047563.2:n.3284G>T
NR_047564.2:n.3492G>T

Protein change:

E1087*

Links:

dbSNP: rs62636277

NCBI 1000 Genomes Browser:

rs62636277

Molecular consequence:

NM_001257966.2:c.2129-406G>T - intron variant - [Sequence Ontology: SO:0001627]
NR_047563.2:n.3284G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_047564.2:n.3492G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001193640.2:c.2995G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001257965.2:c.3259G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_201253.3:c.3331G>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Retinitis pigmentosa 12 (RP12)
Synonyms:: RP 12; RP WITH OR WITHOUT PPRPE; RP WITH OR WITHOUT PRESERVED PARAARTERIOLE RETINAL PIGMENT EPITHELIUM; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010818; MedGen: C1838647; Orphanet: 791; OMIM: 600105

Name:: Leber congenital amaurosis 8 (LCA8)
Identifiers:: MONDO: MONDO:0013453; MedGen: C3151202; Orphanet: 65; OMIM: 613835

Recent activity

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Mus musculus microRNA 7018 (Mir7018), microRNA
Mus musculus microRNA 7018 (Mir7018), microRNA
gi|563320287|ref|NR_105985.1|

Nucleotide
DNA-directed RNA polymerase I subunit RPA1 [Homo sapiens]
DNA-directed RNA polymerase I subunit RPA1 [Homo sapiens]
gi|103471997|ref|NP_056240.2|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003523944	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 23, 2021)	germline	clinical testing	PubMed (9) [See all records that cite these PMIDs] 11389483, 10508521, 22065545, 23379534, 25412400, 26957898, 28041643, 29391521, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003523944

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 23, 2021)

germline

clinical testing

PubMed (9)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Leber congenital amaurosis and retinitis pigmentosa with Coats-like exudative vasculopathy are associated with mutations in the crumbs homologue 1 (CRB1) gene.

den Hollander AI, Heckenlively JR, van den Born LI, de Kok YJ, van der Velde-Visser SD, Kellner U, Jurklies B, van Schooneveld MJ, Blankenagel A, Rohrschneider K, Wissinger B, Cruysberg JR, Deutman AF, Brunner HG, Apfelstedt-Sylla E, Hoyng CB, Cremers FP.

Am J Hum Genet. 2001 Jul;69(1):198-203. Epub 2001 May 24. Erratum in: Am J Hum Genet 2001 Nov;69(5):1160.

PubMed [citation]

PMID:: 11389483
PMCID:: PMC1226034

Mutations in a human homologue of Drosophila crumbs cause retinitis pigmentosa (RP12).

den Hollander AI, ten Brink JB, de Kok YJ, van Soest S, van den Born LI, van Driel MA, van de Pol DJ, Payne AM, Bhattacharya SS, Kellner U, Hoyng CB, Westerveld A, Brunner HG, Bleeker-Wagemakers EM, Deutman AF, Heckenlively JR, Cremers FP, Bergen AA.

Nat Genet. 1999 Oct;23(2):217-21.

PubMed [citation]

PMID:: 10508521

See all PubMed Citations (9)

Details of each submission

From Invitae, SCV003523944.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (9)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 99899). This variant is also known as 3466G‚ÜíT. This premature translational stop signal has been observed in individual(s) with Leber congenital amaurosis (PMID: 11389483). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu1111*) in the CRB1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CRB1 are known to be pathogenic (PMID: 10508521, 22065545, 23379534, 25412400, 26957898, 28041643, 29391521).

#	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

Last Updated: Jun 23, 2024

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