Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation

ClinVar Genomic variation as it relates to human health

Advanced search

NM_000321.2(RB1):c.2134T>C (p.Cys712Arg)

Help
Interpretation:
Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
3 (Most recent: Nov 30, 2020)
Last evaluated:
Mar 28, 2019
Accession:
VCV000013092.4
Variation ID:
13092
Description:
single nucleotide variant
Help

NM_000321.2(RB1):c.2134T>C (p.Cys712Arg)

Allele ID
28131
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
13q14.2
Genomic location
13: 48463758 (GRCh38) GRCh38 UCSC
13: 49037894 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000013.10:g.49037894T>C
NC_000013.11:g.48463758T>C
NM_000321.2:c.2134T>C NP_000312.2:p.Cys712Arg missense
... more HGVS
Protein change
C712R
Other names
-
Canonical SPDI
NC_000013.11:48463757:T:C
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA026423
UniProtKB: P06400#VAR_005587
OMIM: 614041.0024
dbSNP: rs137853296
Help

Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 2 criteria provided, single submitter Mar 28, 2019 RCV000013968.3
Likely pathogenic 1 criteria provided, single submitter Mar 9, 2018 RCV000492516.2
Help
Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
RB1 Sufficient evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
1114 1199

Submitted interpretations and evidence

Help
Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Mar 28, 2019)
criteria provided, single submitter
Method: clinical testing
Retinoblastoma
Allele origin: germline
Invitae
Accession: SCV001224741.1
Submitted: (Feb 06, 2020)
Evidence details
Publications
PubMed (9)
Comment:
This sequence change replaces cysteine with arginine at codon 712 of the RB1 protein (p.Cys712Arg). The cysteine residue is highly conserved and there is a … (more)
Likely pathogenic
(Mar 09, 2018)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Ambry Genetics
Accession: SCV000580826.4
Submitted: (Nov 30, 2020)
Evidence details
Publications
PubMed (4)
Comment:
The p.C712R variant (also known as c.2134T>C), located in coding exon 21 of the RB1 gene, results from a T to C substitution at nucleotide … (more)
Pathogenic
(Oct 01, 1999)
no assertion criteria provided
Method: literature only
RETINOBLASTOMA
Allele origin: germline
OMIM
Accession: SCV000034215.1
Submitted: (Dec 30, 2010)
Evidence details
Publications
PubMed (1)

Functional evidence

Help
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

Help
Title Author Journal Year Link
Outcomes of integrating genetics in management of patients with retinoblastoma. Dhar SU Archives of ophthalmology (Chicago, Ill. : 1960) 2011 PMID: 22084214
Low-penetrant RB allele in small-cell cancer shows geldanamycin instability and discordant expression with mutant ras. Park Y Cell cycle (Georgetown, Tex.) 2008 PMID: 18677112
RB1 gene mutation up-date, a meta-analysis based on 932 reported mutations available in a searchable database. Valverde JR BMC genetics 2005 PMID: 16269091
Sensitive multistep clinical molecular screening of 180 unrelated individuals with retinoblastoma detects 36 novel mutations in the RB1 gene. Nichols KE Human mutation 2005 PMID: 15884040
Sensitive and efficient detection of RB1 gene mutations enhances care for families with retinoblastoma. Richter S American journal of human genetics 2003 PMID: 12541220
Novel RB1 gene constitutional mutations found in Polish patients with familial and/or bilateral retinoblastoma. Jakubowska A Human mutation 2001 PMID: 11668642
A possible hot spot in exon 21 of the retinoblastoma gene predisposing to a low penetrant retinoblastoma phenotype? Ahmad NN Ophthalmic genetics 1999 PMID: 10617920
Temperature-sensitive RB mutations linked to incomplete penetrance of familial retinoblastoma in 12 families. Otterson GA American journal of human genetics 1999 PMID: 10486322
Twelve novel RB1 gene mutations in patients with hereditary retinoblastoma. Mutations in brief no. 206. Online. Yilmaz S Human mutation 1998 PMID: 10671068
A novel missense mutation in patients from a retinoblastoma pedigree showing only mild expression of the tumor phenotype. Cowell JK Oncogene 1998 PMID: 9671401

Text-mined citations for rs137853296...

Help
These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Jan 25, 2021