NM_201253.3(CRB1):c.1431del (p.Ser478fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 8, 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:: RCV001057046.6

Allele description [Variation Report for NM_201253.3(CRB1):c.1431del (p.Ser478fs)]

NM_201253.3(CRB1):c.1431del (p.Ser478fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

1q31.3

Genomic location:

Preferred name:

NM_201253.3(CRB1):c.1431del (p.Ser478fs)

HGVS:

NC_000001.11:g.197421259del
NG_008483.2:g.224798del
NM_001193640.2:c.1095del
NM_001257965.2:c.1224del
NM_001257966.2:c.1431del
NM_201253.3:c.1431delMANE SELECT
NP_001180569.1:p.Ser366fs
NP_001244894.1:p.Ser409fs
NP_001244895.1:p.Ser478fs
NP_957705.1:p.Ser478fs
NC_000001.10:g.197390387del
NC_000001.10:g.197390389del
NM_201253.2:c.1431del
NM_201253.2:c.1431delG
NM_201253.3:c.1431delGMANE SELECT
NR_047563.2:n.1592del
NR_047564.2:n.1592del

Protein change:

S366fs

Links:

dbSNP: rs1553260321

NCBI 1000 Genomes Browser:

rs1553260321

Molecular consequence:

NM_001193640.2:c.1095del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001257965.2:c.1224del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001257966.2:c.1431del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_201253.3:c.1431del - frameshift variant - [Sequence Ontology: SO:0001589]
NR_047563.2:n.1592del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_047564.2:n.1592del - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001221518	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 8, 2023)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 10508521, 22065545, 23379534, 25412400, 26957898, 28041643, 29391521, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001221518

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 8, 2023)

germline

clinical testing

PubMed (8)
[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

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

CRB1 mutations in inherited retinal dystrophies.

Bujakowska K, Audo I, Mohand-Saïd S, Lancelot ME, Antonio A, Germain A, Léveillard T, Letexier M, Saraiva JP, Lonjou C, Carpentier W, Sahel JA, Bhattacharya SS, Zeitz C.

Hum Mutat. 2012 Feb;33(2):306-15. doi: 10.1002/humu.21653. Epub 2011 Dec 27. Review.

PubMed [citation]

PMID:: 22065545
PMCID:: PMC3293109

See all PubMed Citations (8)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001221518.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

This premature translational stop signal has been observed in individual(s) with macular dystrophy (PMID: 29391521). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 446253). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser478Profs*24) 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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