NM_201253.3(CRB1):c.1712A>C (p.Glu571Ala) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 21, 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:: RCV002524407.2

Allele description [Variation Report for NM_201253.3(CRB1):c.1712A>C (p.Glu571Ala)]

NM_201253.3(CRB1):c.1712A>C (p.Glu571Ala)

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.1712A>C (p.Glu571Ala)

HGVS:

NC_000001.11:g.197421540A>C
NG_008483.2:g.225079A>C
NM_001193640.2:c.1376A>C
NM_001257965.2:c.1505A>C
NM_001257966.2:c.1712A>C
NM_201253.3:c.1712A>CMANE SELECT
NP_001180569.1:p.Glu459Ala
NP_001244894.1:p.Glu502Ala
NP_001244895.1:p.Glu571Ala
NP_957705.1:p.Glu571Ala
NC_000001.10:g.197390670A>C
NM_201253.2:c.1712A>C
NR_047563.2:n.1873A>C
NR_047564.2:n.1873A>C

Protein change:

E459A

Links:

dbSNP: rs773233587

NCBI 1000 Genomes Browser:

rs773233587

Molecular consequence:

NM_001193640.2:c.1376A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001257965.2:c.1505A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001257966.2:c.1712A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_201253.3:c.1712A>C - missense variant - [Sequence Ontology: SO:0001583]
NR_047563.2:n.1873A>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_047564.2:n.1873A>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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003523992	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 21, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 28041643, 32581362, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003523992

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 21, 2022)

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

Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease.

Carss KJ, Arno G, Erwood M, Stephens J, Sanchis-Juan A, Hull S, Megy K, Grozeva D, Dewhurst E, Malka S, Plagnol V, Penkett C, Stirrups K, Rizzo R, Wright G, Josifova D, Bitner-Glindzicz M, Scott RH, Clement E, Allen L, Armstrong R, Brady AF, et al.

Am J Hum Genet. 2017 Jan 5;100(1):75-90. doi: 10.1016/j.ajhg.2016.12.003. Epub 2016 Dec 29.

PubMed [citation]

PMID:: 28041643
PMCID:: PMC5223092

Whole-genome sequencing of patients with rare diseases in a national health system.

Turro E, Astle WJ, Megy K, Gräf S, Greene D, Shamardina O, Allen HL, Sanchis-Juan A, Frontini M, Thys C, Stephens J, Mapeta R, Burren OS, Downes K, Haimel M, Tuna S, Deevi SVV, Aitman TJ, Bennett DL, Calleja P, Carss K, Caulfield MJ, et al.

Nature. 2020 Jul;583(7814):96-102. doi: 10.1038/s41586-020-2434-2. Epub 2020 Jun 24.

PubMed [citation]

PMID:: 32581362
PMCID:: PMC7610553

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003523992.1

#	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 glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 571 of the CRB1 protein (p.Glu571Ala). This variant is present in population databases (rs773233587, gnomAD 0.0009%). This missense change has been observed in individual(s) with inherited retinal dystrophy (PMID: 28041643, 32581362). ClinVar contains an entry for this variant (Variation ID: 438071). 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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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