NM_000546.6(TP53):c.665C>T (p.Pro222Leu) AND Li-Fraumeni syndrome 1

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Apr 11, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000411498.11

Allele description [Variation Report for NM_000546.6(TP53):c.665C>T (p.Pro222Leu)]

NM_000546.6(TP53):c.665C>T (p.Pro222Leu)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

17p13.1

Genomic location:

Preferred name:

NM_000546.6(TP53):c.665C>T (p.Pro222Leu)

Other names:

p.P222L:CCG>CTG

HGVS:

NC_000017.11:g.7674866G>A
NG_017013.2:g.17685C>T
NM_000546.6:c.665C>TMANE SELECT
NM_001126112.3:c.665C>T
NM_001126113.3:c.665C>T
NM_001126114.3:c.665C>T
NM_001126115.2:c.269C>T
NM_001126116.2:c.269C>T
NM_001126117.2:c.269C>T
NM_001126118.2:c.548C>T
NM_001276695.3:c.548C>T
NM_001276696.3:c.548C>T
NM_001276697.3:c.188C>T
NM_001276698.3:c.188C>T
NM_001276699.3:c.188C>T
NM_001276760.3:c.548C>T
NM_001276761.3:c.548C>T
NP_000537.3:p.Pro222Leu
NP_000537.3:p.Pro222Leu
NP_001119584.1:p.Pro222Leu
NP_001119585.1:p.Pro222Leu
NP_001119586.1:p.Pro222Leu
NP_001119587.1:p.Pro90Leu
NP_001119588.1:p.Pro90Leu
NP_001119589.1:p.Pro90Leu
NP_001119590.1:p.Pro183Leu
NP_001263624.1:p.Pro183Leu
NP_001263625.1:p.Pro183Leu
NP_001263626.1:p.Pro63Leu
NP_001263627.1:p.Pro63Leu
NP_001263628.1:p.Pro63Leu
NP_001263689.1:p.Pro183Leu
NP_001263690.1:p.Pro183Leu
LRG_321t1:c.665C>T
LRG_321:g.17685C>T
LRG_321p1:p.Pro222Leu
NC_000017.10:g.7578184G>A
NM_000546.4:c.665C>T
NM_000546.5:c.665C>T
P04637:p.Pro222Leu
p.P222L

Protein change:

P183L

Links:

UniProtKB: P04637#VAR_045125; dbSNP: rs146340390

NCBI 1000 Genomes Browser:

rs146340390

Molecular consequence:

NM_000546.6:c.665C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.665C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.665C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.665C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126115.2:c.269C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126116.2:c.269C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126117.2:c.269C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.548C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.548C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.548C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276697.3:c.188C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276698.3:c.188C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276699.3:c.188C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.548C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.548C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Li-Fraumeni syndrome 1 (LFS)
Identifiers:: Gene: 553989; MedGen: C1835398; Orphanet: 524; OMIM: 151623

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000487965	Counsyl	criteria provided, single submitter (Counsyl Autosomal Dominant Disease Classification criteria (2015))	Uncertain significance (Dec 18, 2015)	unknown	clinical testing	PubMed (10) [See all records that cite these PMIDs] 17724467, 19336573, 23897043, 20504876, 25742471, 25980754, 20522432, 21232794, 17311302, 15781620 Counsyl Autosomal Dominant Disease Classification criteria (2015), Citation Link,
SCV004017833	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Uncertain significance (Apr 11, 2023)	unknown	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000487965

Counsyl

criteria provided, single submitter

(Counsyl Autosomal Dominant Disease Classification criteria (2015))

Uncertain significance
(Dec 18, 2015)

unknown

clinical testing

PubMed (10)
[See all records that cite these PMIDs]

Counsyl Autosomal Dominant Disease Classification criteria (2015),

Citation Link,

SCV004017833

Myriad Genetics, Inc.

criteria provided, single submitter

(Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))

Uncertain significance
(Apr 11, 2023)

unknown

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Analysis of transactivation capability and conformation of p53 temperature-dependent mutants and their reactivation by amifostine in yeast.

Grochova D, Vankova J, Damborsky J, Ravcukova B, Smarda J, Vojtesek B, Smardova J.

Oncogene. 2008 Feb 21;27(9):1243-52. Epub 2007 Sep 3.

PubMed [citation]

PMID:: 17724467

High incidence of protein-truncating TP53 mutations in BRCA1-related breast cancer.

Holstege H, Joosse SA, van Oostrom CT, Nederlof PM, de Vries A, Jonkers J.

Cancer Res. 2009 Apr 15;69(8):3625-33. doi: 10.1158/0008-5472.CAN-08-3426. Epub 2009 Mar 31.

PubMed [citation]

PMID:: 19336573

See all PubMed Citations (10)

Details of each submission

From Counsyl, SCV000487965.2

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Myriad Genetics, Inc., SCV004017833.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 24, 2024

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