NM_000321.3(RB1):c.2042G>A (p.Trp681Ter) AND Retinoblastoma

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 12, 2022
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:: RCV003101027.3

Allele description [Variation Report for NM_000321.3(RB1):c.2042G>A (p.Trp681Ter)]

NM_000321.3(RB1):c.2042G>A (p.Trp681Ter)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

13q14.2

Genomic location:

Preferred name:

NM_000321.3(RB1):c.2042G>A (p.Trp681Ter)

HGVS:

NC_000013.11:g.48459769G>A
NG_009009.1:g.161023G>A
NM_000321.3:c.2042G>AMANE SELECT
NM_001407165.1:c.2042G>A
NP_000312.2:p.Trp681Ter
NP_000312.2:p.Trp681Ter
NP_001394094.1:p.Trp681Ter
LRG_517t1:c.2042G>A
LRG_517:g.161023G>A
LRG_517p1:p.Trp681Ter
NC_000013.10:g.49033905G>A
NM_000321.2:c.2042G>A

Protein change:

W681*

Molecular consequence:

NM_000321.3:c.2042G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001407165.1:c.2042G>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Retinoblastoma (RB1)
Synonyms:: Eye cancer, retinoblastoma; RETINOBLASTOMA, SOMATIC
Identifiers:: MONDO: MONDO:0008380; MeSH: D012175; MedGen: C0035335; Orphanet: 790; OMIM: 180200; Human Phenotype Ontology: HP:0009919

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003442227	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 12, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 12541220, 17096365, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003442227

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 12, 2022)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

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

Sensitive and efficient detection of RB1 gene mutations enhances care for families with retinoblastoma.

Richter S, Vandezande K, Chen N, Zhang K, Sutherland J, Anderson J, Han L, Panton R, Branco P, Gallie B.

Am J Hum Genet. 2003 Feb;72(2):253-69. Epub 2002 Dec 18.

PubMed [citation]

PMID:: 12541220
PMCID:: PMC379221

Genotype-phenotype correlations in hereditary familial retinoblastoma.

Taylor M, Dehainault C, Desjardins L, Doz F, Levy C, Sastre X, Couturier J, Stoppa-Lyonnet D, Houdayer C, Gauthier-Villars M.

Hum Mutat. 2007 Mar;28(3):284-93.

PubMed [citation]

PMID:: 17096365

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003442227.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with retinoblastoma (PMID: 12541220). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp681*) in 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 (PMID: 17096365).

#	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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