NM_201253.3(CRB1):c.2300T>C (p.Leu767Pro) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 25, 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:: RCV001042149.6

Allele description [Variation Report for NM_201253.3(CRB1):c.2300T>C (p.Leu767Pro)]

NM_201253.3(CRB1):c.2300T>C (p.Leu767Pro)

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.2300T>C (p.Leu767Pro)

HGVS:

NC_000001.11:g.197427625T>C
NG_008483.2:g.231164T>C
NM_001193640.2:c.1964T>C
NM_001257965.2:c.2093T>C
NM_001257966.2:c.2128+5669T>C
NM_201253.3:c.2300T>CMANE SELECT
NP_001180569.1:p.Leu655Pro
NP_001244894.1:p.Leu698Pro
NP_957705.1:p.Leu767Pro
NC_000001.10:g.197396755T>C
NM_201253.2:c.2300T>C
NR_047563.2:n.2253T>C
NR_047564.2:n.2461T>C

Protein change:

L655P

Links:

dbSNP: rs1451348539

NCBI 1000 Genomes Browser:

rs1451348539

Molecular consequence:

NM_001257966.2:c.2128+5669T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001193640.2:c.1964T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001257965.2:c.2093T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_201253.3:c.2300T>C - missense variant - [Sequence Ontology: SO:0001583]
NR_047563.2:n.2253T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_047564.2:n.2461T>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
SCV001205815	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 25, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 17964524, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001205815

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 25, 2024)

germline

clinical testing

PubMed (2)
[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

Leber congenital amaurosis - a model for efficient genetic testing of heterogeneous disorders: LXIV Edward Jackson Memorial Lecture.

Stone EM.

Am J Ophthalmol. 2007 Dec;144(6):791-811. Epub 2007 Oct 26.

PubMed [citation]

PMID:: 17964524

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001205815.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 767 of the CRB1 protein (p.Leu767Pro). This variant is present in population databases (no rsID available, gnomAD 0.006%). This missense change has been observed in individuals with Leber congenital amaurosis or retinitis pigmentosa (PMID: 17964524; Invitae). ClinVar contains an entry for this variant (Variation ID: 840207). 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.

#	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: Oct 26, 2024

ClinVar

Relating variation to medicine