NM_000321.3(RB1):c.411A>T (p.Glu137Asp) AND Retinoblastoma

Clinical significance:Conflicting interpretations of pathogenicity, Benign(2);Uncertain significance(1) (Last evaluated: Dec 3, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000989108.4

Allele description [Variation Report for NM_000321.3(RB1):c.411A>T (p.Glu137Asp)]

NM_000321.3(RB1):c.411A>T (p.Glu137Asp)

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.411A>T (p.Glu137Asp)
HGVS:
  • NC_000013.11:g.48345110A>T
  • NG_009009.1:g.46364A>T
  • NM_000321.3:c.411A>TMANE SELECT
  • NP_000312.2:p.Glu137Asp
  • NP_000312.2:p.Glu137Asp
  • LRG_517t1:c.411A>T
  • LRG_517:g.46364A>T
  • LRG_517p1:p.Glu137Asp
  • NC_000013.10:g.48919246A>T
  • NM_000321.2:c.411A>T
  • P06400:p.Glu137Asp
Protein change:
E137D
Links:
UniProtKB: P06400#VAR_005573; dbSNP: rs3092902
NCBI 1000 Genomes Browser:
rs3092902
Molecular consequence:
  • NM_000321.3:c.411A>T - missense variant - [Sequence Ontology: SO:0001583]

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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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000284626Invitaecriteria provided, single submitter
Benign
(Dec 3, 2020)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV001139307Mendelicscriteria provided, single submitter
Uncertain significance
(May 28, 2019)
unknownclinical testing

Citation Link,

SCV001271623Illumina Clinical Services Laboratory,Illuminacriteria provided, single submitter
Benign
(Oct 9, 2018)
germlineclinical testing

PubMed (7)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Sensitive multistep clinical molecular screening of 180 unrelated individuals with retinoblastoma detects 36 novel mutations in the RB1 gene.

Nichols KE, Houseknecht MD, Godmilow L, Bunin G, Shields C, Meadows A, Ganguly A.

Hum Mutat. 2005 Jun;25(6):566-74.

PubMed [citation]
PMID:
15884040
See all PubMed Citations (8)

Details of each submission

From Invitae, SCV000284626.7

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Mendelics, SCV001139307.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Illumina Clinical Services Laboratory,Illumina, SCV001271623.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (7)

Description

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, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Dec 4, 2021

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