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NM_201253.3(CRB1):c.1844G>A (p.Gly615Asp) AND multiple conditions

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jul 6, 2022
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:
RCV002539742.3

Allele description [Variation Report for NM_201253.3(CRB1):c.1844G>A (p.Gly615Asp)]

NM_201253.3(CRB1):c.1844G>A (p.Gly615Asp)

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.1844G>A (p.Gly615Asp)
HGVS:
  • NC_000001.11:g.197421672G>A
  • NG_008483.2:g.225211G>A
  • NM_001193640.2:c.1508G>A
  • NM_001257965.2:c.1637G>A
  • NM_001257966.2:c.1844G>A
  • NM_201253.3:c.1844G>AMANE SELECT
  • NP_001180569.1:p.Gly503Asp
  • NP_001244894.1:p.Gly546Asp
  • NP_001244895.1:p.Gly615Asp
  • NP_957705.1:p.Gly615Asp
  • NC_000001.10:g.197390802G>A
  • NM_001257966.1:c.1844G>A
  • NR_047564.2:n.2005G>A
Protein change:
G503D
Links:
dbSNP: rs768905244
NCBI 1000 Genomes Browser:
rs768905244
Molecular consequence:
  • NM_001193640.2:c.1508G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001257965.2:c.1637G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001257966.2:c.1844G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_201253.3:c.1844G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_047564.2:n.2005G>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

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003343337Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Jul 6, 2022) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Mutations in CRB1 are a relatively common cause of autosomal recessive early-onset retinal degeneration in the Israeli and Palestinian populations.

Beryozkin A, Zelinger L, Bandah-Rozenfeld D, Harel A, Strom TA, Merin S, Chowers I, Banin E, Sharon D.

Invest Ophthalmol Vis Sci. 2013 Mar 1;54(3):2068-75. doi: 10.1167/iovs.12-11419.

PubMed [citation]
PMID:
23449718

A nationwide genetic analysis of inherited retinal diseases in Israel as assessed by the Israeli inherited retinal disease consortium (IIRDC).

Sharon D, Ben-Yosef T, Goldenberg-Cohen N, Pras E, Gradstein L, Soudry S, Mezer E, Zur D, Abbasi AH, Zeitz C, Cremers FPM, Khan MI, Levy J, Rotenstreich Y, Birk OS, Ehrenberg M, Leibu R, Newman H, Shomron N, Banin E, Perlman I.

Hum Mutat. 2020 Jan;41(1):140-149. doi: 10.1002/humu.23903. Epub 2019 Sep 15.

PubMed [citation]
PMID:
31456290
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003343337.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

ClinVar contains an entry for this variant (Variation ID: 1297153). 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. This variant disrupts the p.Gly615 amino acid residue in CRB1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 23449718, 31456290). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. This variant has not been reported in the literature in individuals affected with CRB1-related conditions. This variant is present in population databases (rs768905244, gnomAD 0.003%). This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 615 of the CRB1 protein (p.Gly615Asp).

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

Last Updated: Sep 29, 2024