NM_000546.6(TP53):c.188C>T (p.Ala63Val) AND Li-Fraumeni syndrome

Clinical significance:Uncertain significance (Last evaluated: Oct 30, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000467874.6

Allele description [Variation Report for NM_000546.6(TP53):c.188C>T (p.Ala63Val)]

NM_000546.6(TP53):c.188C>T (p.Ala63Val)

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.188C>T (p.Ala63Val)
Other names:
p.A63V:GCT>GTT
HGVS:
  • NC_000017.11:g.7676181G>A
  • NC_000017.11:g.7676181G>A
  • NG_017013.2:g.16370C>T
  • NM_000546.5:c.188C>T
  • NM_000546.6:c.188C>TMANE SELECT
  • NM_001126112.3:c.188C>T
  • NM_001126113.3:c.188C>T
  • NM_001126114.3:c.188C>T
  • NM_001126118.2:c.71C>T
  • NM_001276695.3:c.71C>T
  • NM_001276696.3:c.71C>T
  • NM_001276760.3:c.71C>T
  • NM_001276761.3:c.71C>T
  • NP_000537.3:p.Ala63Val
  • NP_000537.3:p.Ala63Val
  • NP_001119584.1:p.Ala63Val
  • NP_001119585.1:p.Ala63Val
  • NP_001119586.1:p.Ala63Val
  • NP_001119590.1:p.Ala24Val
  • NP_001263624.1:p.Ala24Val
  • NP_001263625.1:p.Ala24Val
  • NP_001263689.1:p.Ala24Val
  • NP_001263690.1:p.Ala24Val
  • LRG_321t1:c.188C>T
  • LRG_321t2:c.188C>T
  • LRG_321:g.16370C>T
  • LRG_321p1:p.Ala63Val
  • NC_000017.10:g.7579499G>A
  • NC_000017.10:g.7579499G>A
  • NM_000546.4:c.188C>T
  • NM_001126112.2(TP53):c.188C>T
  • P04637:p.Ala63Val
  • p.A63V
Protein change:
A24V
Links:
UniProtKB: P04637#VAR_044590; dbSNP: rs372201428
NCBI 1000 Genomes Browser:
rs372201428
Molecular consequence:
  • NM_000546.5:c.188C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000546.6:c.188C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126112.3:c.188C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126113.3:c.188C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126114.3:c.188C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126118.2:c.71C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276695.3:c.71C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276696.3:c.71C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276760.3:c.71C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276761.3:c.71C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Li-Fraumeni syndrome (LFS)
Synonyms:
Sarcoma family syndrome of Li and Fraumeni
Identifiers:
MONDO: MONDO:0018875; MedGen: C0085390; OMIM: PS151623

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000545312Invitaecriteria provided, single submitter
Uncertain significance
(Oct 30, 2020)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Understanding the function-structure and function-mutation relationships of p53 tumor suppressor protein by high-resolution missense mutation analysis.

Kato S, Han SY, Liu W, Otsuka K, Shibata H, Kanamaru R, Ishioka C.

Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8424-9. Epub 2003 Jun 25.

PubMed [citation]
PMID:
12826609
PMCID:
PMC166245

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

Details of each submission

From Invitae, SCV000545312.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change replaces alanine with valine at codon 63 of the TP53 protein (p.Ala63Val). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs372201428, ExAC 0.02%). This variant has not been reported in the literature in individuals with TP53-related disease. ClinVar contains an entry for this variant (Variation ID: 182922). An experimental study in yeast has shown that this variant does not impair the transcriptional transactivation activity of the TP53 protein (PMID: 12826609). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Oct 25, 2021

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