NM_000546.6(TP53):c.1040C>A (p.Ala347Asp) AND not provided

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Mar 19, 2021)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000255021.4

Allele description [Variation Report for NM_000546.6(TP53):c.1040C>A (p.Ala347Asp)]

NM_000546.6(TP53):c.1040C>A (p.Ala347Asp)

Gene:
TP53:tumor protein p53 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17p13.1
Genomic location:
Preferred name:
NM_000546.6(TP53):c.1040C>A (p.Ala347Asp)
HGVS:
  • NC_000017.11:g.7670669G>T
  • NG_017013.2:g.21882C>A
  • NM_000546.5:c.1040C>A
  • NM_000546.6:c.1040C>AMANE SELECT
  • NM_001126112.2:c.1040C>A
  • NM_001126113.2:c.*59C>A
  • NM_001126114.2:c.*147C>A
  • NM_001126115.1:c.644C>A
  • NM_001126116.1:c.*147C>A
  • NM_001126117.1:c.*59C>A
  • NM_001126118.1:c.923C>A
  • NM_001276695.2:c.*59C>A
  • NM_001276696.2:c.*147C>A
  • NM_001276697.2:c.563C>A
  • NM_001276698.2:c.*147C>A
  • NM_001276699.2:c.*59C>A
  • NM_001276760.2:c.923C>A
  • NM_001276761.2:c.923C>A
  • NP_000537.3:p.Ala347Asp
  • NP_000537.3:p.Ala347Asp
  • NP_001119584.1:p.Ala347Asp
  • NP_001119587.1:p.Ala215Asp
  • NP_001119590.1:p.Ala308Asp
  • NP_001263626.1:p.Ala188Asp
  • NP_001263689.1:p.Ala308Asp
  • NP_001263690.1:p.Ala308Asp
  • LRG_321t1:c.1040C>A
  • LRG_321t2:c.1040C>A
  • LRG_321t3:c.*147C>A
  • LRG_321t4:c.*59C>A
  • LRG_321t5:c.644C>A
  • LRG_321t6:c.*147C>A
  • LRG_321t7:c.*59C>A
  • LRG_321t8:c.923C>A
  • LRG_321:g.21882C>A
  • LRG_321:p.Ala347Asp
  • LRG_321p1:p.Ala347Asp
  • LRG_321p5:p.Ala215Asp
  • LRG_321p8:p.Ala308Asp
  • NC_000017.10:g.7573987G>T
  • NM_000546.4:c.1040C>A
  • NM_000546.5(TP53):c.1040C>A
  • c.1040C>A
Protein change:
A188D
Links:
dbSNP: rs397516434
NCBI 1000 Genomes Browser:
rs397516434
Molecular consequence:
  • NM_001126113.2:c.*59C>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_001126114.2:c.*147C>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_001126116.1:c.*147C>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_001126117.1:c.*59C>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_001276695.2:c.*59C>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_001276696.2:c.*147C>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_001276698.2:c.*147C>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_001276699.2:c.*59C>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_000546.5:c.1040C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000546.6:c.1040C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126112.2:c.1040C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126115.1:c.644C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126118.1:c.923C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276697.2:c.563C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276760.2:c.923C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276761.2:c.923C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000321974GeneDxcriteria provided, single submitter
Pathogenic
(Mar 19, 2021)
germlineclinical testing

Citation Link,

SCV000602259Quest Diagnostics Nichols Institute San Juan Capistranocriteria provided, single submitter
Likely pathogenic
(Mar 29, 2017)
germlineclinical testing

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

Summary from all submissions

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

Citations

PubMed

Tetramer formation of tumor suppressor protein p53: Structure, function, and applications.

Kamada R, Toguchi Y, Nomura T, Imagawa T, Sakaguchi K.

Biopolymers. 2016 Nov 4;106(4):598-612. doi: 10.1002/bip.22772. Review.

PubMed [citation]
PMID:
26572807

p53 Proteoforms and Intrinsic Disorder: An Illustration of the Protein Structure-Function Continuum Concept.

Uversky VN.

Int J Mol Sci. 2016 Nov 10;17(11). doi:pii: E1874. Review.

PubMed [citation]
PMID:
27834926
PMCID:
PMC5133874
See all PubMed Citations (7)

Details of each submission

From GeneDx, SCV000321974.8

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

Description

Published functional studies demonstrate a damaging effect: loss of tetramer formation, non-functional transactivation, and reduced growth suppression activity (Kato 2003, Kawaguchi 2005, Fischer 2018) Identified in individuals with Li-Fraumeni syndrome referred for genetic testing at GeneDx and in published literature, segregating with disease in multiple affected individuals from a single family (Villani 2016) Not observed in large population cohorts (Lek 2016) In silico analysis supports that this missense variant does not alter protein structure/function This variant is associated with the following publications: (PMID: 29955864, 26447779, 27496084, 27501770, 27834926, 26572807, 16007150, 12826609)

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

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000602259.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (7)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Aug 17, 2021

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