NM_201253.3(CRB1):c.3055_3059dup (p.Met1020fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 9, 2023
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:: RCV003808686.2

Allele description [Variation Report for NM_201253.3(CRB1):c.3055_3059dup (p.Met1020fs)]

NM_201253.3(CRB1):c.3055_3059dup (p.Met1020fs)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

1q31.3

Genomic location:

Preferred name:

NM_201253.3(CRB1):c.3055_3059dup (p.Met1020fs)

HGVS:

NC_000001.11:g.197434918_197434922dup
NG_008483.2:g.238457_238461dup
NG_008483.3:g.238416_238420dup
NM_001193640.2:c.2719_2723dup
NM_001257965.2:c.2983_2987dup
NM_001257966.2:c.2129-682_2129-678dup
NM_201253.3:c.3055_3059dupMANE SELECT
NP_001180569.1:p.Met908fs
NP_001244894.1:p.Met996fs
NP_957705.1:p.Met1020fs
NC_000001.10:g.197404046_197404047insTTATA
NC_000001.10:g.197404048_197404052dup
NR_047563.2:n.3008_3012dup
NR_047564.2:n.3216_3220dup

Protein change:

M1020fs

Molecular consequence:

NM_001193640.2:c.2719_2723dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001257965.2:c.2983_2987dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_201253.3:c.3055_3059dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001257966.2:c.2129-682_2129-678dup - intron variant - [Sequence Ontology: SO:0001627]
NR_047563.2:n.3008_3012dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_047564.2:n.3216_3220dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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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hypothetical protein Csa_011976 [Cucumis sativus]
hypothetical protein Csa_011976 [Cucumis sativus]
gi|700200402|gb|KGN55560.1||gnl|WGS |CsaV3_4P037830.1.cds1

Protein
JGI_CAAO4030.fwd NIH_XGC_tropTe5 Xenopus tropicalis cDNA clone CAAO4030 5', mRNA...
JGI_CAAO4030.fwd NIH_XGC_tropTe5 Xenopus tropicalis cDNA clone CAAO4030 5', mRNA sequence
gi|58724581|gnl|dbEST|27641742|gb|C 23.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004594876	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 9, 2023)	germline	clinical testing	PubMed (9) [See all records that cite these PMIDs] 35119454, 10508521, 22065545, 23379534, 25412400, 26957898, 28041643, 29391521, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004594876

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 9, 2023)

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

Impact of Next Generation Sequencing in Unraveling the Genetics of 1036 Spanish Families With Inherited Macular Dystrophies.

Del Pozo-Valero M, Riveiro-Alvarez R, Martin-Merida I, Blanco-Kelly F, Swafiri S, Lorda-Sanchez I, Trujillo-Tiebas MJ, Carreño E, Jimenez-Rolando B, Garcia-Sandoval B, Corton M, Avila-Fernandez A, Ayuso C.

Invest Ophthalmol Vis Sci. 2022 Feb 1;63(2):11. doi: 10.1167/iovs.63.2.11.

PubMed [citation]

PMID:: 35119454
PMCID:: PMC8819279

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV004594876.1

#	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. This premature translational stop signal has been observed in individual(s) with CRB1-related conditions (PMID: 35119454). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Met1020Ilefs*4) 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: Sep 29, 2024

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