NM_000546.6(TP53):c.134T>C (p.Leu45Pro) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Sep 1, 2022
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:: RCV000235508.12

Allele description [Variation Report for NM_000546.6(TP53):c.134T>C (p.Leu45Pro)]

NM_000546.6(TP53):c.134T>C (p.Leu45Pro)

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.134T>C (p.Leu45Pro)

HGVS:

NC_000017.11:g.7676235A>G
NG_017013.2:g.16316T>C
NM_000546.6:c.134T>CMANE SELECT
NM_001126112.3:c.134T>C
NM_001126113.3:c.134T>C
NM_001126114.3:c.134T>C
NM_001126118.2:c.17T>C
NM_001276695.3:c.17T>C
NM_001276696.3:c.17T>C
NM_001276760.3:c.17T>C
NM_001276761.3:c.17T>C
NP_000537.3:p.Leu45Pro
NP_000537.3:p.Leu45Pro
NP_001119584.1:p.Leu45Pro
NP_001119585.1:p.Leu45Pro
NP_001119586.1:p.Leu45Pro
NP_001119590.1:p.Leu6Pro
NP_001263624.1:p.Leu6Pro
NP_001263625.1:p.Leu6Pro
NP_001263689.1:p.Leu6Pro
NP_001263690.1:p.Leu6Pro
LRG_321t1:c.134T>C
LRG_321:g.16316T>C
LRG_321p1:p.Leu45Pro
NC_000017.10:g.7579553A>G
NM_000546.4:c.134T>C
NM_000546.5:c.134T>C

Protein change:

L45P

Links:

dbSNP: rs879254066

NCBI 1000 Genomes Browser:

rs879254066

Molecular consequence:

NM_000546.6:c.134T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.134T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.134T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.134T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.17T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.17T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.17T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.17T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.17T>C - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000293353	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Uncertain significance (Nov 2, 2015)	germline	clinical testing	Citation Link,
SCV004141816	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Uncertain significance (Sep 1, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000293353

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Uncertain significance
(Nov 2, 2015)

germline

clinical testing

Citation Link,

SCV004141816

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Uncertain significance
(Sep 1, 2022)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From GeneDx, SCV000293353.9

#	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 denoted TP53 c.134T>C at the cDNA level, p.Leu45Pro (L45P) at the protein level, and results in the change of a Leucine to a Proline (CTG>CCG). This variant not, to our knowledge, been published in the literature as either a pathogenic germline variant or a benign polymorphism. TP53 Leu45Pro was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Leucine and Proline differ in some properties, this is considered a semi-conservative amino acid substitution. TP53 Leu45Pro occurs at a position that is not conserved and is located within the region of interaction with HRMT1L2 (UniProt). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether TP53 Leu45Pro is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.

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

From CeGaT Center for Human Genetics Tuebingen, SCV004141816.10

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

Description

TP53: PM2

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

Last Updated: Oct 20, 2024

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