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NM_201253.3(CRB1):c.2308G>A (p.Gly770Ser) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 27, 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:
RCV001069480.5

Allele description [Variation Report for NM_201253.3(CRB1):c.2308G>A (p.Gly770Ser)]

NM_201253.3(CRB1):c.2308G>A (p.Gly770Ser)

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.2308G>A (p.Gly770Ser)
HGVS:
  • NC_000001.11:g.197427633G>A
  • NG_008483.2:g.231172G>A
  • NM_001193640.2:c.1972G>A
  • NM_001257965.2:c.2101G>A
  • NM_001257966.2:c.2128+5677G>A
  • NM_201253.3:c.2308G>AMANE SELECT
  • NP_001180569.1:p.Gly658Ser
  • NP_001244894.1:p.Gly701Ser
  • NP_957705.1:p.Gly770Ser
  • NC_000001.10:g.197396763G>A
  • NM_001257965.2:c.2101G>A
  • NM_201253.2:c.2308G>A
  • NR_047563.2:n.2261G>A
  • NR_047564.2:n.2469G>A
Protein change:
G658S
Links:
dbSNP: rs767648174
NCBI 1000 Genomes Browser:
rs767648174
Molecular consequence:
  • NM_001257966.2:c.2128+5677G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001193640.2:c.1972G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001257965.2:c.2101G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_201253.3:c.2308G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_047563.2:n.2261G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_047564.2:n.2469G>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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001234648Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Jan 27, 2024)
germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Phenotypic features of CRB1-associated early-onset severe retinal dystrophy and the different molecular approaches to identifying the disease-causing variants.

Kousal B, Dudakova L, Gaillyova R, Hejtmankova M, Diblik P, Michaelides M, Liskova P.

Graefes Arch Clin Exp Ophthalmol. 2016 Sep;254(9):1833-9. doi: 10.1007/s00417-016-3358-2. Epub 2016 Apr 25.

PubMed [citation]
PMID:
27113771

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
See all PubMed Citations (5)

Details of each submission

From Invitae, SCV001234648.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 770 of the CRB1 protein (p.Gly770Ser). This variant is present in population databases (rs767648174, gnomAD 0.007%). This missense change has been observed in individual(s) with early-onset severe retinal dystrophy and/or retinitis pigmentosa (PMID: 27113771, 27208204, 28559085, 30576320). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 236478). 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%. For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jul 15, 2024