NM_000546.6(TP53):c.214_215delinsTG (p.Pro72Cys) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 21, 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:: RCV003488410.1

Allele description [Variation Report for NM_000546.6(TP53):c.214_215delinsTG (p.Pro72Cys)]

NM_000546.6(TP53):c.214_215delinsTG (p.Pro72Cys)

Gene:

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

Variant type:

Indel

Cytogenetic location:

17p13.1

Genomic location:

Preferred name:

NM_000546.6(TP53):c.214_215delinsTG (p.Pro72Cys)

Other names:

p.P72C:CCC>TGC

HGVS:

NC_000017.11:g.7676154_7676155delinsCA
NG_017013.2:g.16396_16397delinsTG
NM_000546.6:c.214_215delinsTGMANE SELECT
NM_001126112.3:c.214_215delinsTG
NM_001126113.3:c.214_215delinsTG
NM_001126114.3:c.214_215delinsTG
NM_001126118.2:c.97_98delinsTG
NM_001276695.3:c.97_98delinsTG
NM_001276696.3:c.97_98delinsTG
NM_001276760.3:c.97_98delinsTG
NM_001276761.3:c.97_98delinsTG
NP_000537.3:p.Pro72Cys
NP_000537.3:p.Pro72Cys
NP_001119584.1:p.Pro72Cys
NP_001119585.1:p.Pro72Cys
NP_001119586.1:p.Pro72Cys
NP_001119590.1:p.Pro33Cys
NP_001263624.1:p.Pro33Cys
NP_001263625.1:p.Pro33Cys
NP_001263689.1:p.Pro33Cys
NP_001263690.1:p.Pro33Cys
LRG_321t1:c.214_215delinsTG
LRG_321t2:c.214_215delinsTG
LRG_321:g.16396_16397delinsTG
LRG_321p1:p.Pro72Cys
NC_000017.10:g.7579472_7579473delinsCA
NM_000546.4:c.214_215delCCinsTG
NM_000546.5:c.214_215delCCinsTG
NM_000546.5:c.214_215delinsTG
NM_001126112.2(TP53):c.214_215delinsTG
p.P72C
p.Pro72Cys

Protein change:

P33C

Links:

dbSNP: rs730882014

NCBI 1000 Genomes Browser:

rs730882014

Molecular consequence:

NM_000546.6:c.214_215delinsTG - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.214_215delinsTG - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.214_215delinsTG - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.214_215delinsTG - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.97_98delinsTG - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.97_98delinsTG - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.97_98delinsTG - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.97_98delinsTG - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.97_98delinsTG - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000697436	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Dec 21, 2023)	germline	clinical testing	PubMed (19) [See all records that cite these PMIDs] 17606709, 21343334, 20407015, 26230955, 21519010, 27463065, 25952993, 22186996, 27680515, 27959731, 16818505, 27895058, 30327374, 11782540, 23246812, 22915647, 26585234, 27276561, 37761360 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000697436

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Dec 21, 2023)

germline

clinical testing

PubMed (19)
[See all records that cite these PMIDs]

Citation Link

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

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

Dominant-negative features of mutant TP53 in germline carriers have limited impact on cancer outcomes.

Monti P, Perfumo C, Bisio A, Ciribilli Y, Menichini P, Russo D, Umbach DM, Resnick MA, Inga A, Fronza G.

Mol Cancer Res. 2011 Mar;9(3):271-9. doi: 10.1158/1541-7786.MCR-10-0496. Epub 2011 Feb 22.

PubMed [citation]

PMID:: 21343334
PMCID:: PMC3077904

See all PubMed Citations (19)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000697436.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (19)

Description

Variant summary: TP53 c.214_215delinsTG (p.Pro72Cys) results in a non-conservative amino acid change in the encoded protein sequence. Two of three in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 250672 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. p.Pro72Cys has been reported in the literature in one individuals affected with Colorectal Cancer (Alsolme_2023). The report does not provide unequivocal conclusions about association of the variant with Li-Fraumeni Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 37761360). Seven submitters have cited clinical-significance assessments for this variant to ClinVar after 2014 and classified this variant as uncertain significance (n=6) and likely benign (n=1). Based on the evidence outlined above, the variant was classified as uncertain significance.

#	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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