NM_201253.3(CRB1):c.4043T>C (p.Ile1348Thr) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 1, 2021
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:: RCV001360437.6

Allele description [Variation Report for NM_201253.3(CRB1):c.4043T>C (p.Ile1348Thr)]

NM_201253.3(CRB1):c.4043T>C (p.Ile1348Thr)

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.4043T>C (p.Ile1348Thr)

HGVS:

NC_000001.11:g.197477701T>C
NG_008483.2:g.281240T>C
NM_001193640.2:c.3707T>C
NM_001257965.2:c.3971T>C
NM_001257966.2:c.2435T>C
NM_201253.3:c.4043T>CMANE SELECT
NP_001180569.1:p.Ile1236Thr
NP_001244894.1:p.Ile1324Thr
NP_001244895.1:p.Ile812Thr
NP_957705.1:p.Ile1348Thr
NC_000001.10:g.197446831T>C
NR_047563.2:n.3996T>C
NR_047564.2:n.4446T>C

Protein change:

I1236T

Links:

dbSNP: rs774187022

NCBI 1000 Genomes Browser:

rs774187022

Molecular consequence:

NM_001193640.2:c.3707T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001257965.2:c.3971T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001257966.2:c.2435T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_201253.3:c.4043T>C - missense variant - [Sequence Ontology: SO:0001583]
NR_047563.2:n.3996T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_047564.2:n.4446T>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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Sarcocystis sp. isolate B4 large subunit ribosomal RNA gene, partial sequence
Sarcocystis sp. isolate B4 large subunit ribosomal RNA gene, partial sequence
gi|1476010393|gb|MH898981.1|

Nucleotide
[Lactobacillus] rogosae strain p6-33-X-ATC-9-D5 16S ribosomal RNA gene, partial ...
[Lactobacillus] rogosae strain p6-33-X-ATC-9-D5 16S ribosomal RNA gene, partial sequence
gi|1893901004|gb|MT903056.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001556353	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 1, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001556353

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 1, 2021)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

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, SCV001556353.3

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

Description

This sequence change replaces isoleucine with threonine at codon 1348 of the CRB1 protein (p.Ile1348Thr). The isoleucine residue is moderately conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is present in population databases (rs774187022, ExAC 0.02%). This variant has not been reported in the literature in individuals affected with CRB1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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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