NM_201253.3(CRB1):c.997G>C (p.Gly333Arg) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 18, 2024
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:: RCV001861045.6

Allele description [Variation Report for NM_201253.3(CRB1):c.997G>C (p.Gly333Arg)]

NM_201253.3(CRB1):c.997G>C (p.Gly333Arg)

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.997G>C (p.Gly333Arg)

HGVS:

NC_000001.11:g.197356839G>C
NG_008483.2:g.160378G>C
NM_001193640.2:c.661G>C
NM_001257965.2:c.790G>C
NM_001257966.2:c.997G>C
NM_201253.3:c.997G>CMANE SELECT
NP_001180569.1:p.Gly221Arg
NP_001244894.1:p.Gly264Arg
NP_001244895.1:p.Gly333Arg
NP_957705.1:p.Gly333Arg
NC_000001.10:g.197325969G>C
NM_201253.2:c.997G>C
NR_047563.2:n.1158G>C
NR_047564.2:n.1158G>C

Protein change:

G221R

Links:

dbSNP: rs778232235

NCBI 1000 Genomes Browser:

rs778232235

Molecular consequence:

NM_001193640.2:c.661G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001257965.2:c.790G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001257966.2:c.997G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_201253.3:c.997G>C - missense variant - [Sequence Ontology: SO:0001583]
NR_047563.2:n.1158G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_047564.2:n.1158G>C - 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

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002310184	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 18, 2024)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 21602930, 18682808, 25412400, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002310184

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 18, 2024)

germline

clinical testing

PubMed (4)
[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

Detection of variants in 15 genes in 87 unrelated Chinese patients with Leber congenital amaurosis.

Li L, Xiao X, Li S, Jia X, Wang P, Guo X, Jiao X, Zhang Q, Hejtmancik JF.

PLoS One. 2011;6(5):e19458. doi: 10.1371/journal.pone.0019458. Epub 2011 May 13.

PubMed [citation]

PMID:: 21602930
PMCID:: PMC3094346

Molecular characterization of Leber congenital amaurosis in Koreans.

Seong MW, Kim SY, Yu YS, Hwang JM, Kim JY, Park SS.

Mol Vis. 2008 Aug 4;14:1429-36.

PubMed [citation]

PMID:: 18682808
PMCID:: PMC2493025

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002310184.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 333 of the CRB1 protein (p.Gly333Arg). This variant is present in population databases (rs778232235, gnomAD 0.006%). This missense change has been observed in individuals with inherited retinal dystrophy (PMID: 21602930; Invitae). ClinVar contains an entry for this variant (Variation ID: 1301835). 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%. This variant disrupts the p.Gly333 amino acid residue in CRB1. Other variant(s) that disrupt this residue have been observed in individuals with CRB1-related conditions (PMID: 18682808, 25412400), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as 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

ClinVar

Relating variation to medicine