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NM_000546.6(TP53):c.638G>T (p.Arg213Leu) AND Li-Fraumeni syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Mar 14, 2020
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:
RCV001371092.7

Allele description [Variation Report for NM_000546.6(TP53):c.638G>T (p.Arg213Leu)]

NM_000546.6(TP53):c.638G>T (p.Arg213Leu)

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.638G>T (p.Arg213Leu)
HGVS:
  • NC_000017.11:g.7674893C>A
  • NG_017013.2:g.17658G>T
  • NM_000546.6:c.638G>TMANE SELECT
  • NM_001126112.3:c.638G>T
  • NM_001126113.3:c.638G>T
  • NM_001126114.3:c.638G>T
  • NM_001126115.2:c.242G>T
  • NM_001126116.2:c.242G>T
  • NM_001126117.2:c.242G>T
  • NM_001126118.2:c.521G>T
  • NM_001276695.3:c.521G>T
  • NM_001276696.3:c.521G>T
  • NM_001276697.3:c.161G>T
  • NM_001276698.3:c.161G>T
  • NM_001276699.3:c.161G>T
  • NM_001276760.3:c.521G>T
  • NM_001276761.3:c.521G>T
  • NP_000537.3:p.Arg213Leu
  • NP_001119584.1:p.Arg213Leu
  • NP_001119585.1:p.Arg213Leu
  • NP_001119586.1:p.Arg213Leu
  • NP_001119587.1:p.Arg81Leu
  • NP_001119588.1:p.Arg81Leu
  • NP_001119589.1:p.Arg81Leu
  • NP_001119590.1:p.Arg174Leu
  • NP_001263624.1:p.Arg174Leu
  • NP_001263625.1:p.Arg174Leu
  • NP_001263626.1:p.Arg54Leu
  • NP_001263627.1:p.Arg54Leu
  • NP_001263628.1:p.Arg54Leu
  • NP_001263689.1:p.Arg174Leu
  • NP_001263690.1:p.Arg174Leu
  • LRG_321:g.17658G>T
  • NC_000017.10:g.7578211C>A
Protein change:
R174L
Links:
dbSNP: rs587778720
NCBI 1000 Genomes Browser:
rs587778720
Molecular consequence:
  • NM_000546.6:c.638G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126112.3:c.638G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126113.3:c.638G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126114.3:c.638G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126115.2:c.242G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126116.2:c.242G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126117.2:c.242G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126118.2:c.521G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276695.3:c.521G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276696.3:c.521G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276697.3:c.161G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276698.3:c.161G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276699.3:c.161G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276760.3:c.521G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276761.3:c.521G>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
SCV001567646Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Uncertain significance
(Mar 14, 2020)
germlineclinical testing

PubMed (8)
[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

Germline TP53 mutations in BRCA1 and BRCA2 mutation-negative French Canadian breast cancer families.

Arcand SL, Maugard CM, Ghadirian P, Robidoux A, Perret C, Zhang P, Fafard E, Mes-Masson AM, Foulkes WD, Provencher D, Narod SA, Tonin PN.

Breast Cancer Res Treat. 2008 Apr;108(3):399-408. Epub 2007 May 31.

PubMed [citation]
PMID:
17541742

Late-onset common cancers in a kindred with an Arg213Gln TP53 germline mutation.

Ruijs MW, Verhoef S, Wigbout G, Pruntel R, Floore AN, de Jong D, van T Veer LJ, Menko FH.

Fam Cancer. 2006;5(2):169-74.

PubMed [citation]
PMID:
16736287
See all PubMed Citations (8)

Details of each submission

From Invitae, SCV001567646.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (8)

Description

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. This variant disrupts the p.Arg213 amino acid residue in TP53. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 17541742, 16736287, 20505364, 16861262, 17724467, 12826609). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. This variant has been reported to affect TP53 protein function (PMID: 12826609, 21514416). This variant has not been reported in the literature in individuals with TP53-related disease. ClinVar contains an entry for this variant (Variation ID: 376650). This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with leucine at codon 213 of the TP53 protein (p.Arg213Leu). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and leucine.

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

Last Updated: Jul 15, 2024