NM_000321.3(RB1):c.110_122del (p.Ser37fs) AND Retinoblastoma

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 3, 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:: RCV003514943.2

Allele description [Variation Report for NM_000321.3(RB1):c.110_122del (p.Ser37fs)]

NM_000321.3(RB1):c.110_122del (p.Ser37fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

13q14.2

Genomic location:

Preferred name:

NM_000321.3(RB1):c.110_122del (p.Ser37fs)

HGVS:

NC_000013.11:g.48304022_48304034del
NG_009009.1:g.5276_5288del
NG_127783.1:g.518_530del
NM_000321.3:c.110_122delMANE SELECT
NM_001407165.1:c.110_122del
NM_001407166.1:c.110_122del
NM_001407167.1:c.110_122del
NP_000312.2:p.Ser37Thrfs
NP_000312.2:p.Ser37fs
NP_001394094.1:p.Ser37fs
NP_001394095.1:p.Ser37fs
NP_001394096.1:p.Ser37fs
LRG_517t1:c.110_122del
LRG_517:g.5276_5288del
LRG_517p1:p.Ser37Thrfs
NC_000013.10:g.48878157_48878169del
NC_000013.10:g.48878158_48878170del
NM_000321.2:c.110_122delGCGGCCCGGAGGA

Protein change:

S37fs

Molecular consequence:

NM_000321.3:c.110_122del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407165.1:c.110_122del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407166.1:c.110_122del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407167.1:c.110_122del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV004312282	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 3, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 17096365, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004312282

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 3, 2023)

germline

clinical testing

PubMed (2)
[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

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

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, SCV004312282.1

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with RB1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser37Thrfs*24) 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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