NM_000546.6(TP53):c.710T>A (p.Met237Lys) AND Li-Fraumeni syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 24, 2023
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:: RCV002524697.5

Allele description [Variation Report for NM_000546.6(TP53):c.710T>A (p.Met237Lys)]

NM_000546.6(TP53):c.710T>A (p.Met237Lys)

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.710T>A (p.Met237Lys)

HGVS:

NC_000017.11:g.7674253A>T
NG_017013.2:g.18298T>A
NM_000546.6:c.710T>AMANE SELECT
NM_001126112.3:c.710T>A
NM_001126113.3:c.710T>A
NM_001126114.3:c.710T>A
NM_001126115.2:c.314T>A
NM_001126116.2:c.314T>A
NM_001126117.2:c.314T>A
NM_001126118.2:c.593T>A
NM_001276695.3:c.593T>A
NM_001276696.3:c.593T>A
NM_001276697.3:c.233T>A
NM_001276698.3:c.233T>A
NM_001276699.3:c.233T>A
NM_001276760.3:c.593T>A
NM_001276761.3:c.593T>A
NP_000537.3:p.Met237Lys
NP_001119584.1:p.Met237Lys
NP_001119585.1:p.Met237Lys
NP_001119586.1:p.Met237Lys
NP_001119587.1:p.Met105Lys
NP_001119588.1:p.Met105Lys
NP_001119589.1:p.Met105Lys
NP_001119590.1:p.Met198Lys
NP_001263624.1:p.Met198Lys
NP_001263625.1:p.Met198Lys
NP_001263626.1:p.Met78Lys
NP_001263627.1:p.Met78Lys
NP_001263628.1:p.Met78Lys
NP_001263689.1:p.Met198Lys
NP_001263690.1:p.Met198Lys
LRG_321:g.18298T>A
NC_000017.10:g.7577571A>T
NM_000546.6:c.710T>A

Protein change:

M105K

Links:

dbSNP: rs765848205

NCBI 1000 Genomes Browser:

rs765848205

Molecular consequence:

NM_000546.6:c.710T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.710T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.710T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.710T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126115.2:c.314T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126116.2:c.314T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126117.2:c.314T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.593T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.593T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.593T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276697.3:c.233T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276698.3:c.233T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276699.3:c.233T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.593T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.593T>A - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003255718	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 24, 2023)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 11370630, 17606709, 21343334, 12826609, 22109999, 29979965, 30224644, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003255718

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 24, 2023)

germline

clinical testing

PubMed (8)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Detection of 11 germline inactivating TP53 mutations and absence of TP63 and HCHK2 mutations in 17 French families with Li-Fraumeni or Li-Fraumeni-like syndrome.

Bougeard G, Limacher JM, Martin C, Charbonnier F, Killian A, Delattre O, Longy M, Jonveaux P, Fricker JP, Stoppa-Lyonnet D, Flaman JM, Frébourg T.

J Med Genet. 2001 Apr;38(4):253-7. No abstract available.

PubMed [citation]

PMID:: 11370630
PMCID:: PMC1734839

Transcriptional functionality of germ line p53 mutants influences cancer phenotype.

Monti P, Ciribilli Y, Jordan J, Menichini P, Umbach DM, Resnick MA, Luzzatto L, Inga A, Fronza G.

Clin Cancer Res. 2007 Jul 1;13(13):3789-95.

PubMed [citation]

PMID:: 17606709
PMCID:: PMC2128783

See all PubMed Citations (8)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003255718.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 12826609, 29979965, 30224644) indicates that this missense variant is expected to disrupt TP53 function. ClinVar contains an entry for this variant (Variation ID: 376636). This missense change has been observed in individual(s) with TP53-related conditions (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces methionine, which is neutral and non-polar, with lysine, which is basic and polar, at codon 237 of the TP53 protein (p.Met237Lys). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Met237 amino acid residue in TP53. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11370630, 12826609, 17606709, 21343334, 29979965, 30224644; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this missense change affects TP53 function (PMID: 12826609, 22109999, 29979965, 30224644).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Mar 16, 2025

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