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NM_000321.2(RB1):c.411A>T (p.Glu137Asp)

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Interpretation:
Conflicting interpretations of pathogenicity​

Benign(2);Likely benign(2);Uncertain significance(1)

Review status:
criteria provided, conflicting interpretations
Submissions:
6 (Most recent: Dec 11, 2020)
Last evaluated:
Apr 7, 2020
Accession:
VCV000041684.8
Variation ID:
41684
Description:
single nucleotide variant
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NM_000321.2(RB1):c.411A>T (p.Glu137Asp)

Allele ID
50123
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
13q14.2
Genomic location
13: 48345110 (GRCh38) GRCh38 UCSC
13: 48919246 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000013.10:g.48919246A>T
NC_000013.11:g.48345110A>T
NM_000321.2:c.411A>T NP_000312.2:p.Glu137Asp missense
... more HGVS
Protein change
E137D
Other names
-
Canonical SPDI
NC_000013.11:48345109:A:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD), exomes 0.00034
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00069
Exome Aggregation Consortium (ExAC) 0.00042
Trans-Omics for Precision Medicine (TOPMed) 0.00042
The Genome Aggregation Database (gnomAD) 0.00051
Links
ClinGen: CA026455
UniProtKB: P06400#VAR_005573
dbSNP: rs3092902
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Likely benign 1 criteria provided, single submitter Aug 27, 2018 RCV000570544.2
Likely benign 1 criteria provided, single submitter Apr 7, 2020 RCV001285704.1
Conflicting interpretations of pathogenicity 3 criteria provided, conflicting interpretations Dec 31, 2019 RCV000989108.3
Uncertain significance 1 no assertion criteria provided Jul 13, 2012 RCV000034596.3
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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

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Uncertain significance
(May 28, 2019)
criteria provided, single submitter
Method: clinical testing
Retinoblastoma
Allele origin: unknown
Mendelics
Accession: SCV001139307.1
Submitted: (Oct 22, 2019)
Evidence details
Benign
(Dec 31, 2019)
criteria provided, single submitter
Method: clinical testing
Retinoblastoma
Allele origin: germline
Invitae
Accession: SCV000284626.6
Submitted: (Jan 29, 2020)
Evidence details
Benign
(Oct 09, 2018)
criteria provided, single submitter
Method: clinical testing
Retinoblastoma
Allele origin: germline
Illumina Clinical Services Laboratory,Illumina
Accession: SCV001271623.1
Submitted: (Feb 20, 2020)
Evidence details
Publications
PubMed (7)
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
Likely benign
(Aug 27, 2018)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Ambry Genetics
Accession: SCV000664578.3
Submitted: (Nov 30, 2020)
Evidence details
Publications
PubMed (5)
Comment:
Co-occurence with a mutation in another gene that clearly explains a proband's phenotype;Other data supporting benign classification
Likely benign
(Apr 07, 2020)
criteria provided, single submitter
Method: clinical testing
none provided
Allele origin: germline
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories
Accession: SCV001472180.1
Submitted: (Dec 11, 2020)
Evidence details
variant of unknown significance
(Jul 13, 2012)
no assertion criteria provided
Method: research
not provided
Allele origin: germline
Biesecker Lab/Clinical Genomics Section,National Institutes of Health
Study: ClinSeq
Accession: SCV000043463.1
Submitted: (Jul 15, 2012)
Evidence details
Publications
PubMed (1)
Comment:
Converted during submission to Uncertain significance.

Functional evidence

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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

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Title Author Journal Year Link
Evaluation of ACMG-Guideline-Based Variant Classification of Cancer Susceptibility and Non-Cancer-Associated Genes in Families Affected by Breast Cancer. Maxwell KN American journal of human genetics 2016 PMID: 27153395
Secondary variants in individuals undergoing exome sequencing: screening of 572 individuals identifies high-penetrance mutations in cancer-susceptibility genes. Johnston JJ American journal of human genetics 2012 PMID: 22703879
Exploring the structural and functional effect of pRB by significant nsSNP in the coding region of RB1 gene causing retinoblastoma. Rajasekaran R Science China. Life sciences 2010 PMID: 20596833
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
Conservation of the RB1 gene in human and primates. Sivakumaran TA Human mutation 2005 PMID: 15776430
Constitutional RB1-gene mutations in patients with isolated unilateral retinoblastoma. Lohmann DR American journal of human genetics 1997 PMID: 9311732
Spectrum of germline mutations in the RB1 gene: a study of 232 patients with hereditary and non hereditary retinoblastoma. Blanquet V Human molecular genetics 1995 PMID: 7795591
Identification of germline mutations in the RB1 gene by denaturant gradient gel electrophoresis and polymerase chain reaction direct sequencing. Blanquet V Human molecular genetics 1993 PMID: 8364580

Text-mined citations for rs3092902...

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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 30, 2021