NM_000321.2(RB1):c.1654C>T (p.Arg552Ter) AND Retinoblastoma

This record was updated by the submitter. Please see the current version.

Germline classification:: Conflicting classifications of pathogenicity (3 submissions)
Last evaluated:: Jan 9, 2017
Review status:: criteria provided, conflicting classifications

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:: RCV000114733.2

Allele description

NM_000321.2(RB1):c.1654C>T (p.Arg552Ter)

Gene:

RB1:RB transcriptional corepressor 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

13q14.2

Genomic location:

Preferred name:

NM_000321.2(RB1):c.1654C>T (p.Arg552Ter)

Other names:

L11910:g.78238C>T

HGVS:

NC_000013.11:g.48381402C>T
NG_009009.1:g.82656C>T
NM_000321.2:c.1654C>T
NP_000312.2:p.Arg552Ter
LRG_517t1:c.1654C>T
LRG_517:g.82656C>T
LRG_517p1:p.Arg552Ter
NC_000013.10:g.48955538C>T

Protein change:

R552*

Links:

dbSNP: rs121913303

NCBI 1000 Genomes Browser:

rs121913303

Molecular consequence:

NM_000321.2:c.1654C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Retinoblastoma (RB1)
Synonyms:: RETINOBLASTOMA, SOMATIC
Identifiers:: MeSH: D012175; MedGen: C0035335; Orphanet: 790; OMIM: 180200

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000087356	Genetic Diagnostic Laboratory,University of Pennsylvania School of Medicine	no assertion criteria provided	Pathogenic (Sep 16, 2013)	somatic	research
SCV000504839	Database of Curated Mutations (DoCM)	no assertion criteria provided	Likely pathogenic (Jul 14, 2015)	somatic	literature only	PubMed (2) [See all records that cite these PMIDs] 25157968, 25754945 Citation Link,
SCV000551833	Invitae,	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 9, 2017)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000087356

Genetic Diagnostic Laboratory,University of Pennsylvania School of Medicine

no assertion criteria provided

Pathogenic
(Sep 16, 2013)

somatic

research

SCV000504839

Database of Curated Mutations (DoCM)

no assertion criteria provided

Likely pathogenic
(Jul 14, 2015)

somatic

literature only

PubMed (2)
[See all records that cite these PMIDs]

Citation Link,

SCV000551833

Invitae,

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 9, 2017)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	somatic	yes	not provided	not provided	not provided	not provided	not provided	research, literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Prospective enterprise-level molecular genotyping of a cohort of cancer patients.

MacConaill LE, Garcia E, Shivdasani P, Ducar M, Adusumilli R, Breneiser M, Byrne M, Chung L, Conneely J, Crosby L, Garraway LA, Gong X, Hahn WC, Hatton C, Kantoff PW, Kluk M, Kuo F, Jia Y, Joshi R, Longtine J, Manning A, Palescandolo E, et al.

J Mol Diagn. 2014 Nov;16(6):660-72. doi: 10.1016/j.jmoldx.2014.06.004. Epub 2014 Aug 23.

PubMed [citation]

PMID:: 25157968
PMCID:: PMC4210463

Genetic screening in patients with Retinoblastoma in Israel.

Sagi M, Frenkel A, Eilat A, Weinberg N, Frenkel S, Pe'er J, Abeliovich D, Lerer I.

Fam Cancer. 2015 Sep;14(3):471-80. doi: 10.1007/s10689-015-9794-z.

PubMed [citation]

PMID:: 25754945

Details of each submission

From Genetic Diagnostic Laboratory,University of Pennsylvania School of Medicine, SCV000087356.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	somatic	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Database of Curated Mutations (DoCM), SCV000504839.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (2)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	somatic	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Invitae,, SCV000551833.1

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

Description

This sequence change creates a premature translational stop signal at codon 552 (p.Arg552*) of the RB1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RB1 are known to be pathogenic. This particular variant has been reported in the literature in several patients affected with retinoblastoma (PMID: 7704558, 27582626, 22219649, 24791139, 25754945). For these reasons, this variant has been classified as 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: Dec 19, 2017

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