NM_201253.3(CRB1):c.3145T>C (p.Ser1049Pro) AND multiple conditions

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Dec 11, 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:: RCV002594786.3

Allele description [Variation Report for NM_201253.3(CRB1):c.3145T>C (p.Ser1049Pro)]

NM_201253.3(CRB1):c.3145T>C (p.Ser1049Pro)

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.3145T>C (p.Ser1049Pro)

HGVS:

NC_000001.11:g.197435008T>C
NG_008483.2:g.238547T>C
NG_008483.3:g.238506T>C
NM_001193640.2:c.2809T>C
NM_001257965.2:c.3073T>C
NM_001257966.2:c.2129-592T>C
NM_201253.3:c.3145T>CMANE SELECT
NP_001180569.1:p.Ser937Pro
NP_001244894.1:p.Ser1025Pro
NP_957705.1:p.Ser1049Pro
NC_000001.10:g.197404138T>C
NR_047563.2:n.3098T>C
NR_047564.2:n.3306T>C

Protein change:

S1025P

Molecular consequence:

NM_001257966.2:c.2129-592T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001193640.2:c.2809T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001257965.2:c.3073T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_201253.3:c.3145T>C - missense variant - [Sequence Ontology: SO:0001583]
NR_047563.2:n.3098T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_047564.2:n.3306T>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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gi|2744122044|gb|CP157903.1|

Nucleotide
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Silene noctiflora isolate:OPL-1.1
Silene noctiflora isolate:OPL-1.1 Genome sequencing and assembly

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Hylarana latouchii
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Hylarana latouchii RefSeq Genome

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002957744	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Dec 11, 2023)	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

SCV002957744

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Dec 11, 2023)

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, SCV002957744.2

#	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 serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 1049 of the CRB1 protein (p.Ser1049Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with retinitis pigmentosa (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 1919368). 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 80%. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been 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: Sep 29, 2024

ClinVar

Relating variation to medicine