NM_000546.5(TP53):c.848G>A (p.Arg283His) AND Li-Fraumeni syndrome 1

Clinical significance:Uncertain significance (Last evaluated: Feb 6, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000507738.2

Allele description [Variation Report for NM_000546.5(TP53):c.848G>A (p.Arg283His)]

NM_000546.5(TP53):c.848G>A (p.Arg283His)

Gene:
TP53:tumor protein p53 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17p13.1
Genomic location:
Preferred name:
NM_000546.5(TP53):c.848G>A (p.Arg283His)
Other names:
p.R283H:CGC>CAC
HGVS:
  • NC_000017.11:g.7673772C>T
  • NG_017013.2:g.18779G>A
  • NM_000546.5:c.848G>A
  • NM_001126112.2:c.848G>A
  • NM_001126113.2:c.848G>A
  • NM_001126114.2:c.848G>A
  • NM_001126115.1:c.452G>A
  • NM_001126116.1:c.452G>A
  • NM_001126117.1:c.452G>A
  • NM_001126118.1:c.731G>A
  • NM_001276695.2:c.731G>A
  • NM_001276696.2:c.731G>A
  • NM_001276697.2:c.371G>A
  • NM_001276698.2:c.371G>A
  • NM_001276699.2:c.371G>A
  • NM_001276760.2:c.731G>A
  • NM_001276761.2:c.731G>A
  • NP_000537.3:p.Arg283His
  • NP_001119584.1:p.Arg283His
  • NP_001119585.1:p.Arg283His
  • NP_001119586.1:p.Arg283His
  • NP_001119587.1:p.Arg151His
  • NP_001119588.1:p.Arg151His
  • NP_001119589.1:p.Arg151His
  • NP_001119590.1:p.Arg244His
  • NP_001263624.1:p.Arg244His
  • NP_001263625.1:p.Arg244His
  • NP_001263626.1:p.Arg124His
  • NP_001263627.1:p.Arg124His
  • NP_001263628.1:p.Arg124His
  • NP_001263689.1:p.Arg244His
  • NP_001263690.1:p.Arg244His
  • LRG_321t1:c.848G>A
  • LRG_321t2:c.848G>A
  • LRG_321t3:c.848G>A
  • LRG_321t4:c.848G>A
  • LRG_321t5:c.452G>A
  • LRG_321t6:c.452G>A
  • LRG_321t7:c.452G>A
  • LRG_321t8:c.731G>A
  • LRG_321:g.18779G>A
  • LRG_321:p.Arg283His
  • LRG_321p1:p.Arg283His
  • LRG_321p3:p.Arg283His
  • LRG_321p4:p.Arg283His
  • LRG_321p5:p.Arg151His
  • LRG_321p6:p.Arg151His
  • LRG_321p7:p.Arg151His
  • LRG_321p8:p.Arg244His
  • NC_000017.10:g.7577090C>T
  • NM_000546.4:c.848G>A
  • P04637:p.Arg283His
  • p.R283H
Protein change:
R124H
Links:
UniProtKB: P04637#VAR_006019; dbSNP: rs371409680
NCBI 1000 Genomes Browser:
rs371409680
Molecular consequence:
  • NM_000546.5:c.848G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126112.2:c.848G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126113.2:c.848G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126114.2:c.848G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126115.1:c.452G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126116.1:c.452G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126117.1:c.452G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126118.1:c.731G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276695.2:c.731G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276696.2:c.731G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276697.2:c.371G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276698.2:c.371G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276699.2:c.371G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276760.2:c.731G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276761.2:c.731G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Li-Fraumeni syndrome 1 (LFS)
Synonyms:
Li-Fraumeni syndrome 3
Identifiers:
Gene: 553989; MONDO: MONDO:0007903; MedGen: C1835398; Orphanet: 524; OMIM: 151623

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000605420ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratoriescriteria provided, single submitter
Uncertain significance
(Feb 6, 2020)
germlineclinical testing

Citation Link

Summary from all submissions

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

Details of each submission

From ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories, SCV000605420.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The TP53 c.848G>A; p.Arg283His variant (rs371409680), is reported in the literature in individuals affected with an astrocytoma or a glioblastoma (Fulci 2002, Ishii 1999) and in an individual with breast cancer (Susswein 2016). This variant is reported as likely pathogenic/uncertain significance by multiple laboratories in ClinVar (Variation ID: 142324), and is found in the general population with an overall allele frequency of 0.004% (10/ 251,452 alleles) in the Genome Aggregation Database. The arginine at codon 283 is moderately conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Functional analyses of the variant protein show variable results, although many show decreased transactivation and a moderate dominant-negative effect (see link TP53MutLoad database, Campomenosi 2001, Crook 1998, Di Como 1998, Flaman 1998, Fulci 2002). Additionally, recent analyses of Genome Aggregation Database frequency compared to affected individuals do not reach a consensus as to the clinical significance (Evans 2019, Fortuno 2019, Soussi 2019). Therefore, due to conflicting results, the clinical significance of this variant is uncertain.

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

Last Updated: May 27, 2021

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