NM_000546.6(TP53):c.722C>T (p.Ser241Phe) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Sep 9, 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:: RCV003114189.6

Allele description [Variation Report for NM_000546.6(TP53):c.722C>T (p.Ser241Phe)]

NM_000546.6(TP53):c.722C>T (p.Ser241Phe)

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.722C>T (p.Ser241Phe)

HGVS:

NC_000017.11:g.7674241G>A
NG_017013.2:g.18310C>T
NM_000546.6:c.722C>TMANE SELECT
NM_001126112.3:c.722C>T
NM_001126113.3:c.722C>T
NM_001126114.3:c.722C>T
NM_001126115.2:c.326C>T
NM_001126116.2:c.326C>T
NM_001126117.2:c.326C>T
NM_001126118.2:c.605C>T
NM_001276695.3:c.605C>T
NM_001276696.3:c.605C>T
NM_001276697.3:c.245C>T
NM_001276698.3:c.245C>T
NM_001276699.3:c.245C>T
NM_001276760.3:c.605C>T
NM_001276761.3:c.605C>T
NP_000537.3:p.Ser241Phe
NP_000537.3:p.Ser241Phe
NP_001119584.1:p.Ser241Phe
NP_001119585.1:p.Ser241Phe
NP_001119586.1:p.Ser241Phe
NP_001119587.1:p.Ser109Phe
NP_001119588.1:p.Ser109Phe
NP_001119589.1:p.Ser109Phe
NP_001119590.1:p.Ser202Phe
NP_001263624.1:p.Ser202Phe
NP_001263625.1:p.Ser202Phe
NP_001263626.1:p.Ser82Phe
NP_001263627.1:p.Ser82Phe
NP_001263628.1:p.Ser82Phe
NP_001263689.1:p.Ser202Phe
NP_001263690.1:p.Ser202Phe
LRG_321t1:c.722C>T
LRG_321:g.18310C>T
LRG_321p1:p.Ser241Phe
NC_000017.10:g.7577559G>A
NM_000546.4:c.722C>T
NM_000546.5:c.722C>T
P04637:p.Ser241Phe
p.S241F

Protein change:

S109F; SER241PHE

Links:

UniProtKB: P04637#VAR_005969; OMIM: 191170.0013; dbSNP: rs28934573

NCBI 1000 Genomes Browser:

rs28934573

Molecular consequence:

NM_000546.6:c.722C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.722C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.722C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.722C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126115.2:c.326C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126116.2:c.326C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126117.2:c.326C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.605C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.605C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.605C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276697.3:c.245C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276698.3:c.245C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276699.3:c.245C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.605C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.605C>T - missense variant - [Sequence Ontology: SO:0001583]

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
SCV003798846	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Aug 3, 2022)	germline	clinical testing	Citation Link,
SCV004221371	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Pathogenic (Sep 9, 2022)	unknown	clinical testing	PubMed (20) [See all records that cite these PMIDs] 1565143, 8401536, 8633021, 17606709, 19556618, 20128691, 21343334, 22887876, 23031740, 26585234, 26911350, 27189670, 28975465, 29979965, 30224644, 31775759, 32475984, 32817165, 33087929, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003798846

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Aug 3, 2022)

germline

clinical testing

Citation Link,

SCV004221371

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Pathogenic
(Sep 9, 2022)

unknown

clinical testing

PubMed (20)
[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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Prevalence and spectrum of germline mutations of the p53 gene among patients with sarcoma.

Toguchida J, Yamaguchi T, Dayton SH, Beauchamp RL, Herrera GE, Ishizaki K, Yamamuro T, Meyers PA, Little JB, Sasaki MS, et al.

N Engl J Med. 1992 May 14;326(20):1301-8.

PubMed [citation]

PMID:: 1565143

Screening for TP53 mutations in osteosarcomas using constant denaturant gel electrophoresis (CDGE).

Smith-Sørensen B, Gebhardt MC, Kloen P, McIntyre J, Aguilar F, Cerutti P, Børresen AL.

Hum Mutat. 1993;2(4):274-85.

PubMed [citation]

PMID:: 8401536

See all PubMed Citations (20)

Details of each submission

From GeneDx, SCV003798846.2

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

Description

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Published functional studies demonstrate a damaging effect: impaired DNA binding and transcriptional activation (Malcikova et al., 2010; Kotler et al., 2018); Observed in individuals with TP53-related cancers (Toguchida et al., 1992; Gonzalez et al., 2009; Mannan et al., 2016; Kwong et al., 2020); This variant is associated with the following publications: (PMID: 21343334, 1565143, 17606709, 23031740, 30840781, 31105275, 19225112, 26585234, 20128691, 29979965, 22887876, 32475984, 15510160, 33087929, 30720243, 26911350, 33138793, 28975465, 19556618, 29070607, 32817165)

#	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 Quest Diagnostics Nichols Institute San Juan Capistrano, SCV004221371.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (20)

Description

The frequency of this variant in the general population, 0.000004 (1/251476 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported in affected individuals with Li-Fraumeni syndrome (LFS) (PMIDs: 17606709 (2007), 23031740 (2012), 26911350 (2016), 28975465 (2017), and 32817165 (2020)). Functional studies demonstrated decreased DNA binding, transactivation activity, a dominant negative effect, and reduced solubility compared to wild type (PMIDs: 8633021 (1996), 20128691 (2010), 21343334 (2011), 29979965 (2018), 30224644 (2018), 32475984 (2020)). Three de novo cases have been identified (PMIDs: 1565143 (1992), 19556618 (2009), and 22887876 (2012)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is damaging. Based on the available information, this variant is classified as pathogenic.

#	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 10, 2024

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