NM_201253.3(CRB1):c.1690G>T (p.Asp564Tyr) AND Retinal dystrophy

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Mar 6, 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:: RCV004579629.2

Allele description [Variation Report for NM_201253.3(CRB1):c.1690G>T (p.Asp564Tyr)]

NM_201253.3(CRB1):c.1690G>T (p.Asp564Tyr)

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.1690G>T (p.Asp564Tyr)

HGVS:

NC_000001.11:g.197421518G>T
NG_008483.2:g.225057G>T
NG_008483.3:g.225016G>T
NM_001193640.2:c.1354G>T
NM_001257965.2:c.1483G>T
NM_001257966.2:c.1690G>T
NM_201253.3:c.1690G>TMANE SELECT
NP_001180569.1:p.Asp452Tyr
NP_001244894.1:p.Asp495Tyr
NP_001244895.1:p.Asp564Tyr
NP_957705.1:p.Asp564Tyr
NC_000001.10:g.197390648G>T
NR_047563.2:n.1851G>T
NR_047564.2:n.1851G>T

Protein change:

D452Y

Molecular consequence:

NM_001193640.2:c.1354G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001257965.2:c.1483G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001257966.2:c.1690G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_201253.3:c.1690G>T - missense variant - [Sequence Ontology: SO:0001583]
NR_047563.2:n.1851G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_047564.2:n.1851G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Retinal dystrophy
Synonyms:: Inherited retinal dystrophy
Identifiers:: MONDO: MONDO:0019118; MeSH: D058499; MedGen: C0854723; Human Phenotype Ontology: HP:0000556

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Peroxiredoxin 3 [Homo sapiens]
Peroxiredoxin 3 [Homo sapiens]
gi|18203832|gb|AAH21691.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV005062111	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely pathogenic (Mar 6, 2024)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 18055816, 35672425, 35551639, 23379534 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005062111

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely pathogenic
(Mar 6, 2024)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

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

Mutation screening of 299 Spanish families with retinal dystrophies by Leber congenital amaurosis genotyping microarray.

Vallespin E, Cantalapiedra D, Riveiro-Alvarez R, Wilke R, Aguirre-Lamban J, Avila-Fernandez A, Lopez-Martinez MA, Gimenez A, Trujillo-Tiebas MJ, Ramos C, Ayuso C.

Invest Ophthalmol Vis Sci. 2007 Dec;48(12):5653-61.

PubMed [citation]

PMID:: 18055816

Clinical exome sequencing for inherited retinal degenerations at a tertiary care center.

Ganapathi M, Thomas-Wilson A, Buchovecky C, Dharmadhikari A, Barua S, Lee W, Ruan MZC, Soucy M, Ragi S, Tanaka J, Clark LN, Naini AB, Liao J, Mansukhani M, Tsang S, Jobanputra V.

Sci Rep. 2022 Jun 7;12(1):9358. doi: 10.1038/s41598-022-13026-2.

PubMed [citation]

PMID:: 35672425
PMCID:: PMC9174483

See all PubMed Citations (4)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV005062111.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

Variant summary: CRB1 c.1690G>T (p.Asp564Tyr) results in a non-conservative amino acid change located in the Laminin G domain (IPR001791) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251246 control chromosomes (gnomAD). c.1690G>T has been reported in the literature in individuals affected with Leber congenital amaurosis and Retinitis pigmentosa (examples: Vallespin_2007, Corton_2013, Bouzidi_2021, Ganapathi_2022). These data indicate that the variant is likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 35551639, 23379534, 35672425, 18055816). No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as likely 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: Nov 10, 2024

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