NM_201253.3(CRB1):c.1360G>A (p.Gly454Arg) AND multiple conditions

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Nov 24, 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:: RCV002651385.5

Allele description [Variation Report for NM_201253.3(CRB1):c.1360G>A (p.Gly454Arg)]

NM_201253.3(CRB1):c.1360G>A (p.Gly454Arg)

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.1360G>A (p.Gly454Arg)

HGVS:

NC_000001.11:g.197421188G>A
NG_008483.3:g.224686G>A
NM_001193640.2:c.1024G>A
NM_001257965.2:c.1153G>A
NM_001257966.2:c.1360G>A
NM_201253.2:c.1360G>A
NM_201253.3:c.1360G>AMANE SELECT
NP_001180569.1:p.Gly342Arg
NP_001244894.1:p.Gly385Arg
NP_001244895.1:p.Gly454Arg
NP_957705.1:p.Gly454Arg
NC_000001.10:g.197390318G>A
NG_008483.2:g.224727G>A
NM_201253.3:c.1360G>A
NR_047563.2:n.1521G>A
NR_047564.2:n.1521G>A

Protein change:

G342R

Molecular consequence:

NM_001193640.2:c.1024G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001257965.2:c.1153G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001257966.2:c.1360G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_201253.3:c.1360G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_047563.2:n.1521G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_047564.2:n.1521G>A - 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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Statice salsuginosa (0)
Nucleotide
transcription factor bHLH95 [Citrus x clementina]
transcription factor bHLH95 [Citrus x clementina]
gi|1350328006|ref|XP_024035248.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003523370	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Nov 24, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 20079931, 35119454, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003523370

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Nov 24, 2023)

germline

clinical testing

PubMed (3)
[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

Visual acuity in patients with Leber's congenital amaurosis and early childhood-onset retinitis pigmentosa.

Walia S, Fishman GA, Jacobson SG, Aleman TS, Koenekoop RK, Traboulsi EI, Weleber RG, Pennesi ME, Heon E, Drack A, Lam BL, Allikmets R, Stone EM.

Ophthalmology. 2010 Jun;117(6):1190-8. doi: 10.1016/j.ophtha.2009.09.056. Epub 2010 Jan 15.

PubMed [citation]

PMID:: 20079931

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

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003523370.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 454 of the CRB1 protein (p.Gly454Arg). This variant is present in population databases (no rsID available, gnomAD 0.007%). This missense change has been observed in individuals with CRB1-related conditions (PMID: 20079931, 35119454). ClinVar contains an entry for this variant (Variation ID: 2202907). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CRB1 protein function with a positive predictive value of 95%. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

#	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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