NM_000546.6(TP53):c.322_339del (p.Gly108_Phe113del) AND Li-Fraumeni syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 5, 2021
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:: RCV001855008.5

Allele description [Variation Report for NM_000546.6(TP53):c.322_339del (p.Gly108_Phe113del)]

NM_000546.6(TP53):c.322_339del (p.Gly108_Phe113del)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

17p13.1

Genomic location:

Preferred name:

NM_000546.6(TP53):c.322_339del (p.Gly108_Phe113del)

HGVS:

NC_000017.11:g.7676031_7676048del
NG_017013.2:g.16504_16521del
NM_000546.6:c.322_339delMANE SELECT
NM_001126112.3:c.322_339del
NM_001126113.3:c.322_339del
NM_001126114.3:c.322_339del
NM_001126118.2:c.205_222del
NM_001276695.3:c.205_222del
NM_001276696.3:c.205_222del
NM_001276760.3:c.205_222del
NM_001276761.3:c.205_222del
NP_000537.3:p.Gly108_Phe113del
NP_001119584.1:p.Gly108_Phe113del
NP_001119585.1:p.Gly108_Phe113del
NP_001119586.1:p.Gly108_Phe113del
NP_001119590.1:p.Gly69_Phe74del
NP_001263624.1:p.Gly69_Phe74del
NP_001263625.1:p.Gly69_Phe74del
NP_001263689.1:p.Gly69_Phe74del
NP_001263690.1:p.Gly69_Phe74del
LRG_321:g.16504_16521del
NC_000017.10:g.7579348_7579365del
NC_000017.10:g.7579349_7579366del
NM_000546.4:c.322_339delGGTTTCCGTCTGGGCTTC

Links:

dbSNP: rs886039495

NCBI 1000 Genomes Browser:

rs886039495

Molecular consequence:

NM_000546.6:c.322_339del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001126112.3:c.322_339del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001126113.3:c.322_339del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001126114.3:c.322_339del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001126118.2:c.205_222del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001276695.3:c.205_222del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001276696.3:c.205_222del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001276760.3:c.205_222del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001276761.3:c.205_222del - 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
SCV002133055	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 5, 2021)	germline	clinical testing	PubMed (9) [See all records that cite these PMIDs] 12826609, 16778209, 21445056, 21552135, 23894400, 23897043, 24076587, 29070607, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002133055

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 5, 2021)

germline

clinical testing

PubMed (9)
[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

Understanding the function-structure and function-mutation relationships of p53 tumor suppressor protein by high-resolution missense mutation analysis.

Kato S, Han SY, Liu W, Otsuka K, Shibata H, Kanamaru R, Ishioka C.

Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8424-9. Epub 2003 Jun 25.

PubMed [citation]

PMID:: 12826609
PMCID:: PMC166245

Mutant p53 induces the GEF-H1 oncogene, a guanine nucleotide exchange factor-H1 for RhoA, resulting in accelerated cell proliferation in tumor cells.

Mizuarai S, Yamanaka K, Kotani H.

Cancer Res. 2006 Jun 15;66(12):6319-26.

PubMed [citation]

PMID:: 16778209

See all PubMed Citations (9)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002133055.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (9)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the TP53 protein in which other variant(s) (p.Arg110Pro) have been determined to be pathogenic (PMID: 12826609, 16778209, 21445056, 21552135, 23894400, 23897043, 24076587, 29070607; Invitae). 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: 265351). 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.322_339del, results in the deletion of 6 amino acid(s) of the TP53 protein (p.Gly108_Phe113del), but otherwise preserves the integrity of the reading frame.

#	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

ClinVar

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