NM_201253.3(CRB1):c.2309G>A (p.Gly770Asp) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 10, 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:: RCV003323464.2

Allele description [Variation Report for NM_201253.3(CRB1):c.2309G>A (p.Gly770Asp)]

NM_201253.3(CRB1):c.2309G>A (p.Gly770Asp)

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.2309G>A (p.Gly770Asp)

HGVS:

NC_000001.11:g.197427634G>A
NG_008483.2:g.231173G>A
NM_001193640.2:c.1973G>A
NM_001257965.2:c.2102G>A
NM_001257966.2:c.2128+5678G>A
NM_201253.3:c.2309G>AMANE SELECT
NP_001180569.1:p.Gly658Asp
NP_001244894.1:p.Gly701Asp
NP_957705.1:p.Gly770Asp
NC_000001.10:g.197396764G>A
NM_201253.2:c.2309G>A
NR_047563.2:n.2262G>A
NR_047564.2:n.2470G>A

Protein change:

G658D

Links:

dbSNP: rs878853365

NCBI 1000 Genomes Browser:

rs878853365

Molecular consequence:

NM_001257966.2:c.2128+5678G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001193640.2:c.1973G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001257965.2:c.2102G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_201253.3:c.2309G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_047563.2:n.2262G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_047564.2:n.2470G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004029977	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Jul 10, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004029977

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Jul 10, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link

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

Molecular findings from 537 individuals with inherited retinal disease.

Ellingford JM, Barton S, Bhaskar S, O'Sullivan J, Williams SG, Lamb JA, Panda B, Sergouniotis PI, Gillespie RL, Daiger SP, Hall G, Gale T, Lloyd IC, Bishop PN, Ramsden SC, Black GCM.

J Med Genet. 2016 Nov;53(11):761-767. doi: 10.1136/jmedgenet-2016-103837. Epub 2016 May 11.

PubMed [citation]

PMID:: 27208204
PMCID:: PMC5106339

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004029977.1

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

Description

Variant summary: CRB1 c.2309G>A (p.Gly770Asp) results in a non-conservative amino acid change located in the Laminin G domain (IPR001791) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 250752 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.2309G>A has been reported in the literature in at least one compound heterozygous individual affected with Retinal Dystrophy (e.g., Ellingford_2016). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication was ascertained in the context of this evaluation (PMID: 27208204). No submitters have reported clinical-significance assessments for this variant to ClinVar after 2014. Additionally, another missense variant impacting the same codon, c.2308G>A (p.G770S), has been reported in the literature in patients affected with retinal dystrophy (PMIDs: 27208204, 30576320, 31879567) and reported as pathogenic in ClinVar. Based on the evidence outlined above, the variant was classified as VUS-possibly 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: Jun 23, 2024

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