NM_000546.6(TP53):c.870_871delinsAC (p.Lys291Gln) AND Li-Fraumeni syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 5, 2016
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:: RCV000471030.6

Allele description [Variation Report for NM_000546.6(TP53):c.870_871delinsAC (p.Lys291Gln)]

NM_000546.6(TP53):c.870_871delinsAC (p.Lys291Gln)

Gene:

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

Variant type:

Indel

Cytogenetic location:

17p13.1

Genomic location:

Preferred name:

NM_000546.6(TP53):c.870_871delinsAC (p.Lys291Gln)

HGVS:

NC_000017.11:g.7673749_7673750delinsGT
NG_017013.2:g.18801_18802delinsAC
NM_000546.6:c.870_871delinsACMANE SELECT
NM_001126112.3:c.870_871delinsAC
NM_001126113.3:c.870_871delinsAC
NM_001126114.3:c.870_871delinsAC
NM_001126115.2:c.474_475delinsAC
NM_001126116.2:c.474_475delinsAC
NM_001126117.2:c.474_475delinsAC
NM_001126118.2:c.753_754delinsAC
NM_001276695.3:c.753_754delinsAC
NM_001276696.3:c.753_754delinsAC
NM_001276697.3:c.393_394delinsAC
NM_001276698.3:c.393_394delinsAC
NM_001276699.3:c.393_394delinsAC
NM_001276760.3:c.753_754delinsAC
NM_001276761.3:c.753_754delinsAC
NP_000537.3:p.Lys291Gln
NP_001119584.1:p.Lys291Gln
NP_001119585.1:p.Lys291Gln
NP_001119586.1:p.Lys291Gln
NP_001119587.1:p.Lys159Gln
NP_001119588.1:p.Lys159Gln
NP_001119589.1:p.Lys159Gln
NP_001119590.1:p.Lys252Gln
NP_001263624.1:p.Lys252Gln
NP_001263625.1:p.Lys252Gln
NP_001263626.1:p.Lys132Gln
NP_001263627.1:p.Lys132Gln
NP_001263628.1:p.Lys132Gln
NP_001263689.1:p.Lys252Gln
NP_001263690.1:p.Lys252Gln
LRG_321:g.18801_18802delinsAC
NC_000017.10:g.7577067_7577068delinsGT
NM_000546.5:c.870_871delCAinsAC

Protein change:

K132Q

Links:

dbSNP: rs1060501205

NCBI 1000 Genomes Browser:

rs1060501205

Molecular consequence:

NM_000546.6:c.870_871delinsAC - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.870_871delinsAC - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.870_871delinsAC - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.870_871delinsAC - missense variant - [Sequence Ontology: SO:0001583]
NM_001126115.2:c.474_475delinsAC - missense variant - [Sequence Ontology: SO:0001583]
NM_001126116.2:c.474_475delinsAC - missense variant - [Sequence Ontology: SO:0001583]
NM_001126117.2:c.474_475delinsAC - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.753_754delinsAC - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.753_754delinsAC - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.753_754delinsAC - missense variant - [Sequence Ontology: SO:0001583]
NM_001276697.3:c.393_394delinsAC - missense variant - [Sequence Ontology: SO:0001583]
NM_001276698.3:c.393_394delinsAC - missense variant - [Sequence Ontology: SO:0001583]
NM_001276699.3:c.393_394delinsAC - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.753_754delinsAC - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.753_754delinsAC - 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
SCV000545338	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 5, 2016)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 15781620, 12826609, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000545338

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 5, 2016)

germline

clinical testing

PubMed (3)
[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

Lack of correlation between p53-dependent transcriptional activity and the ability to induce apoptosis among 179 mutant p53s.

Kakudo Y, Shibata H, Otsuka K, Kato S, Ishioka C.

Cancer Res. 2005 Mar 15;65(6):2108-14.

PubMed [citation]

PMID:: 15781620

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

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000545338.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

In summary, this variant is a novel change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies have shown that this missense change does not reduce the ability of TP53 to induce apoptosis or affect the transcriptional transactivation activity of the TP53 protein (PMID: 15781620, 12826609). This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a TP53-related disease. This sequence change replaces lysine with glutamine at codon 291 of the TP53 protein (p.Lys291Gln). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and glutamine.

#	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: Sep 29, 2024

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