NM_201253.3(CRB1):c.1405T>G (p.Cys469Gly) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 6, 2023
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:: RCV002614384.3

Allele description [Variation Report for NM_201253.3(CRB1):c.1405T>G (p.Cys469Gly)]

NM_201253.3(CRB1):c.1405T>G (p.Cys469Gly)

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.1405T>G (p.Cys469Gly)

HGVS:

NC_000001.11:g.197421233T>G
NG_008483.2:g.224772T>G
NG_008483.3:g.224731T>G
NM_001193640.2:c.1069T>G
NM_001257965.2:c.1198T>G
NM_001257966.2:c.1405T>G
NM_201253.3:c.1405T>GMANE SELECT
NP_001180569.1:p.Cys357Gly
NP_001244894.1:p.Cys400Gly
NP_001244895.1:p.Cys469Gly
NP_957705.1:p.Cys469Gly
NC_000001.10:g.197390363T>G
NR_047563.2:n.1566T>G
NR_047564.2:n.1566T>G

Protein change:

C357G

Molecular consequence:

NM_001193640.2:c.1069T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001257965.2:c.1198T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001257966.2:c.1405T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_201253.3:c.1405T>G - missense variant - [Sequence Ontology: SO:0001583]
NR_047563.2:n.1566T>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_047564.2:n.1566T>G - 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

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mothers against decapentaplegic homolog 3 isoform 1 [Homo sapiens]
mothers against decapentaplegic homolog 3 isoform 1 [Homo sapiens]
gi|5174513|ref|NP_005893.1|

Protein
Mus musculus carbonic anhydrase 1, mRNA (cDNA clone MGC:164063 IMAGE:40130709), ...
Mus musculus carbonic anhydrase 1, mRNA (cDNA clone MGC:164063 IMAGE:40130709), complete cds
gi|124376423|gb|BC132432.1|

Nucleotide
Homo sapiens mitochondrial ribosomal protein S11, mRNA (cDNA clone MGC:22144 IMA...
Homo sapiens mitochondrial ribosomal protein S11, mRNA (cDNA clone MGC:22144 IMAGE:4452949), complete cds
gi|15214710|gb|BC012489.1|

Nucleotide
Chain AS, 60S ribosomal protein L18a
Chain AS, 60S ribosomal protein L18a
gi|1979407780|pdb|5AJ0|AS

Protein
Malignant tumor of ascending colon
Malignant tumor of ascending colon

MedGen

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002965736	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 6, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 31630094, 33970760, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002965736

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 6, 2023)

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

Genetic and clinical findings in a Chinese cohort with Leber congenital amaurosis and early onset severe retinal dystrophy.

Xu K, Xie Y, Sun T, Zhang X, Chen C, Li Y.

Br J Ophthalmol. 2020 Jul;104(7):932-937. doi: 10.1136/bjophthalmol-2019-314281. Epub 2019 Oct 19.

PubMed [citation]

PMID:: 31630094

Molecular genetics with clinical characteristics of Leber congenital amaurosis in the Han population of western China.

Zhu L, Ouyang W, Zhang M, Wang H, Li S, Meng X, Yin ZQ.

Ophthalmic Genet. 2021 Aug;42(4):392-401. doi: 10.1080/13816810.2021.1904417. Epub 2021 May 10.

PubMed [citation]

PMID:: 33970760

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002965736.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 1928144). This missense change has been observed in individual(s) with retinal dystrophy (PMID: 31630094, 33970760). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with glycine, which is neutral and non-polar, at codon 469 of the CRB1 protein (p.Cys469Gly).

#	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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