NM_000546.6(TP53):c.529_546del (p.Pro177_Cys182del) AND Li-Fraumeni syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 19, 2024
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:: RCV001042929.10

Allele description [Variation Report for NM_000546.6(TP53):c.529_546del (p.Pro177_Cys182del)]

NM_000546.6(TP53):c.529_546del (p.Pro177_Cys182del)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

17p13.1

Genomic location:

Preferred name:

NM_000546.6(TP53):c.529_546del (p.Pro177_Cys182del)

HGVS:

NC_000017.11:g.7675073_7675090del
NG_017013.2:g.17468_17485del
NM_000546.4:c.529_546delCCCCACCATGAGCGCTGC
NM_000546.6:c.529_546delMANE SELECT
NM_001126112.3:c.529_546del
NM_001126113.3:c.529_546del
NM_001126114.3:c.529_546del
NM_001126115.2:c.133_150del
NM_001126116.2:c.133_150del
NM_001126117.2:c.133_150del
NM_001126118.2:c.412_429del
NM_001276695.3:c.412_429del
NM_001276696.3:c.412_429del
NM_001276697.3:c.52_69del
NM_001276698.3:c.52_69del
NM_001276699.3:c.52_69del
NM_001276760.3:c.412_429del
NM_001276761.3:c.412_429del
NP_000537.3:p.Pro177_Cys182del
NP_001119584.1:p.Pro177_Cys182del
NP_001119585.1:p.Pro177_Cys182del
NP_001119586.1:p.Pro177_Cys182del
NP_001119587.1:p.Pro45_Cys50del
NP_001119588.1:p.Pro45_Cys50del
NP_001119589.1:p.Pro45_Cys50del
NP_001119590.1:p.Pro138_Cys143del
NP_001263624.1:p.Pro138_Cys143del
NP_001263625.1:p.Pro138_Cys143del
NP_001263626.1:p.Pro18_Cys23del
NP_001263627.1:p.Pro18_Cys23del
NP_001263628.1:p.Pro18_Cys23del
NP_001263689.1:p.Pro138_Cys143del
NP_001263690.1:p.Pro138_Cys143del
LRG_321t1:c.529_546del
LRG_321:g.17468_17485del
NC_000017.10:g.7578384_7578401del
NC_000017.10:g.7578391_7578408del
NM_000546.5:c.529_546del
NM_000546.6:c.529_546del

Links:

dbSNP: rs2073361326

Molecular consequence:

NM_000546.6:c.529_546del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001126112.3:c.529_546del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001126113.3:c.529_546del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001126114.3:c.529_546del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001126115.2:c.133_150del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001126116.2:c.133_150del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001126117.2:c.133_150del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001126118.2:c.412_429del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001276695.3:c.412_429del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001276696.3:c.412_429del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001276697.3:c.52_69del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001276698.3:c.52_69del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001276699.3:c.52_69del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001276760.3:c.412_429del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001276761.3:c.412_429del - 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
SCV001206638	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 19, 2024)	germline	clinical testing	PubMed (10) [See all records that cite these PMIDs] 29489754, 33138793, 33245408, 12826609, 20421238, 26787237, 27501770, 27873457, 30224644, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001206638

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 19, 2024)

germline

clinical testing

PubMed (10)
[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

The landscape of genomic alterations across childhood cancers.

Gröbner SN, Worst BC, Weischenfeldt J, Buchhalter I, Kleinheinz K, Rudneva VA, Johann PD, Balasubramanian GP, Segura-Wang M, Brabetz S, Bender S, Hutter B, Sturm D, Pfaff E, Hübschmann D, Zipprich G, Heinold M, Eils J, Lawerenz C, Erkek S, Lambo S, Waszak S, et al.

Nature. 2018 Mar 15;555(7696):321-327. doi: 10.1038/nature25480. Epub 2018 Feb 28. Erratum in: Nature. 2018 Jul;559(7714):E10. doi: 10.1038/s41586-018-0167-2..

PubMed [citation]

PMID:: 29489754

Mutation screening of germline TP53 mutations in high-risk Chinese breast cancer patients.

Kwong A, Shin VY, Ho CYS, Au CH, Slavin TP, Weitzel JN, Chan TL, Ma ESK.

BMC Cancer. 2020 Nov 2;20(1):1053. doi: 10.1186/s12885-020-07476-y.

PubMed [citation]

PMID:: 33138793
PMCID:: PMC7607817

See all PubMed Citations (10)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001206638.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (10)

Description

This variant, c.529_546del, results in the deletion of 6 amino acid(s) of the TP53 protein (p.Pro177_Cys182del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with clinical features of TP53-related conditions (PMID: 29489754, 33138793, 33245408). ClinVar contains an entry for this variant (Variation ID: 840834). This variant disrupts a region of the TP53 protein in which other variant(s) (p.Pro177Arg) have been determined to be pathogenic (PMID: 12826609, 20421238, 26787237, 27501770, 27873457, 30224644; internal data). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. 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: Apr 12, 2026

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