NM_000546.5(TP53):c.398T>C (p.Met133Thr) AND Li-Fraumeni syndrome 1

Clinical significance:Pathogenic (Last evaluated: May 8, 2015)

Review status:(0/4)0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000013151.20

Allele description [Variation Report for NM_000546.5(TP53):c.398T>C (p.Met133Thr)]

NM_000546.5(TP53):c.398T>C (p.Met133Thr)

Gene:
TP53:tumor protein p53 [Gene - OMIM]
Variant type:
single nucleotide variant
Cytogenetic location:
17p13.1
Genomic location:
Preferred name:
NM_000546.5(TP53):c.398T>C (p.Met133Thr)
HGVS:
  • NC_000017.11:g.7675214A>G
  • NG_017013.2:g.17337T>C
  • NM_000546.5:c.398T>C
  • NM_001126112.2:c.398T>C
  • NM_001126113.2:c.398T>C
  • NM_001126114.2:c.398T>C
  • NM_001126115.1:c.2T>C
  • NM_001126116.1:c.2T>C
  • NM_001126117.1:c.2T>C
  • NM_001126118.1:c.281T>C
  • NP_000537.3:p.Met133Thr
  • NP_001119584.1:p.Met133Thr
  • NP_001119585.1:p.Met133Thr
  • NP_001119586.1:p.Met133Thr
  • NP_001119587.1:p.Met1Thr
  • NP_001119588.1:p.Met1Thr
  • NP_001119589.1:p.Met1Thr
  • NP_001119590.1:p.Met94Thr
  • LRG_321t1:c.398T>C
  • LRG_321t2:c.398T>C
  • LRG_321t3:c.398T>C
  • LRG_321t4:c.398T>C
  • LRG_321t5:c.2T>C
  • LRG_321t6:c.2T>C
  • LRG_321t7:c.2T>C
  • LRG_321t8:c.281T>C
  • LRG_321:g.17337T>C
  • LRG_321p1:p.Met133Thr
  • LRG_321p3:p.Met133Thr
  • LRG_321p4:p.Met133Thr
  • LRG_321p5:p.Met1Thr
  • LRG_321p6:p.Met1Thr
  • LRG_321p7:p.Met1Thr
  • LRG_321p8:p.Met94Thr
  • NC_000017.10:g.7578532A>G
Protein change:
M133T; MET133THR
Links:
OMIM: 191170.0011; dbSNP: 28934873
NCBI 1000 Genomes Browser:
rs28934873
Molecular consequence:
  • NM_000546.5:c.398T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276697.1:c.-80T>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]

Condition(s)

Name:
Li-Fraumeni syndrome 1 (LFS1)
Identifiers:
MedGen: C1835398; Orphanet: 524; OMIM: 151623
Age of onset:
Variable

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000033398OMIMno assertion criteria providedPathogenic
(May 8, 2015)
germlineliterature only

PubMed (3)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Mutations in the p53 gene occur in diverse human tumour types.

Nigro JM, Baker SJ, Preisinger AC, Jessup JM, Hostetter R, Cleary K, Bigner SH, Davidson N, Baylin S, Devilee P, et al.

Nature. 1989 Dec 7;342(6250):705-8.

PubMed [citation]
PMID:
2531845

TP53 mutation and haplotype analysis of two large African American families.

Hung J, Mims B, Lozano G, Strong L, Harvey C, Chen TT, Stastny V, Tomlinson G.

Hum Mutat. 1999;14(3):216-21.

PubMed [citation]
PMID:
10477429
See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000033398.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (3)

Description

In 9 members of an extended family with Li-Fraumeni syndrome-1 (151623), Law et al. (1991) found that a germline mutation at codon 133 (ATG-to-ACG), resulting in substitution of threonine for methionine (M133T), completely cosegregated with the cancer syndrome. An ATG-to-TTG mutation at codon 133, resulting in substitution of leucine for methionine, had been reported previously in a sporadic cancer of the colon (Nigro et al., 1989).

Hung et al. (1999) identified the same M133T mutation in the TP53 gene in 2 large, apparently unrelated African American families, both of which had a high incidence of breast cancer and other tumors characteristic of Li-Fraumeni syndrome. Haplotype analysis revealed that the 2 families shared an identical haplotype. Loss of heterozygosity at the TP53 locus in tumor tissue from each family was observed; in each case, the retained allele carried the common haplotype. The frequency of this haplotype in the general African American population is less than 0.003. This unique haplotype, combined with the rare TP53 mutation, suggested that these African American families share a common ancestry. The second proband of Hung et al. (1999) was from the same family as that in which Law et al. (1991) had originally described the M133T mutation in relation to Li-Fraumeni syndrome.

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

Last Updated: Jun 29, 2015