NM_000546.6(TP53):c.737_745del (p.Met246_Arg248del) AND Li-Fraumeni syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 14, 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:: RCV001360150.7

Allele description [Variation Report for NM_000546.6(TP53):c.737_745del (p.Met246_Arg248del)]

NM_000546.6(TP53):c.737_745del (p.Met246_Arg248del)

Gene:

TP53:tumor protein p53 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

17p13.1

Genomic location:

Preferred name:

NM_000546.6(TP53):c.737_745del (p.Met246_Arg248del)

HGVS:

NC_000017.11:g.7674219_7674227del
NG_017013.2:g.18325_18333del
NM_000546.6:c.737_745delMANE SELECT
NM_001126112.3:c.737_745del
NM_001126113.3:c.737_745del
NM_001126114.3:c.737_745del
NM_001126115.2:c.341_349del
NM_001126116.2:c.341_349del
NM_001126117.2:c.341_349del
NM_001126118.2:c.620_628del
NM_001276695.3:c.620_628del
NM_001276696.3:c.620_628del
NM_001276697.3:c.260_268del
NM_001276698.3:c.260_268del
NM_001276699.3:c.260_268del
NM_001276760.3:c.620_628del
NM_001276761.3:c.620_628del
NP_000537.3:p.Met246_Arg248del
NP_001119584.1:p.Met246_Arg248del
NP_001119585.1:p.Met246_Arg248del
NP_001119586.1:p.Met246_Arg248del
NP_001119587.1:p.Met114_Arg116del
NP_001119588.1:p.Met114_Arg116del
NP_001119589.1:p.Met114_Arg116del
NP_001119590.1:p.Met207_Arg209del
NP_001263624.1:p.Met207_Arg209del
NP_001263625.1:p.Met207_Arg209del
NP_001263626.1:p.Met87_Arg89del
NP_001263627.1:p.Met87_Arg89del
NP_001263628.1:p.Met87_Arg89del
NP_001263689.1:p.Met207_Arg209del
NP_001263690.1:p.Met207_Arg209del
LRG_321:g.18325_18333del
NC_000017.10:g.7577536_7577544del
NC_000017.10:g.7577537_7577545del

Links:

dbSNP: rs2151020665

NCBI 1000 Genomes Browser:

rs2151020665

Molecular consequence:

NM_000546.6:c.737_745del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001126112.3:c.737_745del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001126113.3:c.737_745del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001126114.3:c.737_745del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001126115.2:c.341_349del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001126116.2:c.341_349del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001126117.2:c.341_349del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001126118.2:c.620_628del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001276695.3:c.620_628del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001276696.3:c.620_628del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001276697.3:c.260_268del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001276698.3:c.260_268del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001276699.3:c.260_268del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001276760.3:c.620_628del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001276761.3:c.620_628del - inframe_deletion - [Sequence Ontology: SO:0001822]

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
SCV001556053	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 14, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 7887414, 17606709, 21305319, 21601526, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001556053

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 14, 2023)

germline

clinical testing

PubMed (5)
[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

Germ-line p53 mutations in 15 families with Li-Fraumeni syndrome.

Frebourg T, Barbier N, Yan YX, Garber JE, Dreyfus M, Fraumeni J Jr, Li FP, Friend SH.

Am J Hum Genet. 1995 Mar;56(3):608-15.

PubMed [citation]

PMID:: 7887414
PMCID:: PMC1801151

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 (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001556053.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This variant disrupts a region of the TP53 protein in which other variant(s) (p.Arg248Gln) have been determined to be pathogenic (PMID: 7887414, 17606709, 21305319, 21601526). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 1052035). This variant has not been reported in the literature in individuals affected with TP53-related conditions. This variant is not present in population databases (gnomAD no frequency). This variant, c.737_745del, results in the deletion of 3 amino acid(s) of the TP53 protein (p.Met246_Arg248del), but otherwise preserves the integrity of the reading frame. For these reasons, this variant has been classified as Pathogenic.

#	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: Nov 10, 2024

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