NM_000546.6(TP53):c.584T>A (p.Ile195Asn) AND Li-Fraumeni syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 10, 2024
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:: RCV000692717.12

Allele description [Variation Report for NM_000546.6(TP53):c.584T>A (p.Ile195Asn)]

NM_000546.6(TP53):c.584T>A (p.Ile195Asn)

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.584T>A (p.Ile195Asn)

HGVS:

NC_000017.11:g.7674947A>T
NG_017013.2:g.17604T>A
NM_000546.6:c.584T>AMANE SELECT
NM_001126112.3:c.584T>A
NM_001126113.3:c.584T>A
NM_001126114.3:c.584T>A
NM_001126115.2:c.188T>A
NM_001126116.2:c.188T>A
NM_001126117.2:c.188T>A
NM_001126118.2:c.467T>A
NM_001276695.3:c.467T>A
NM_001276696.3:c.467T>A
NM_001276697.3:c.107T>A
NM_001276698.3:c.107T>A
NM_001276699.3:c.107T>A
NM_001276760.3:c.467T>A
NM_001276761.3:c.467T>A
NP_000537.3:p.Ile195Asn
NP_000537.3:p.Ile195Asn
NP_001119584.1:p.Ile195Asn
NP_001119585.1:p.Ile195Asn
NP_001119586.1:p.Ile195Asn
NP_001119587.1:p.Ile63Asn
NP_001119588.1:p.Ile63Asn
NP_001119589.1:p.Ile63Asn
NP_001119590.1:p.Ile156Asn
NP_001263624.1:p.Ile156Asn
NP_001263625.1:p.Ile156Asn
NP_001263626.1:p.Ile36Asn
NP_001263627.1:p.Ile36Asn
NP_001263628.1:p.Ile36Asn
NP_001263689.1:p.Ile156Asn
NP_001263690.1:p.Ile156Asn
LRG_321t1:c.584T>A
LRG_321:g.17604T>A
LRG_321p1:p.Ile195Asn
NC_000017.10:g.7578265A>T
NM_000546.4:c.584T>A
NM_000546.5:c.584T>A

Protein change:

I156N

Links:

dbSNP: rs760043106

NCBI 1000 Genomes Browser:

rs760043106

Molecular consequence:

NM_000546.6:c.584T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.584T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.584T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.584T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126115.2:c.188T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126116.2:c.188T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126117.2:c.188T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.467T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.467T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.467T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276697.3:c.107T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276698.3:c.107T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276699.3:c.107T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.467T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.467T>A - 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
SCV000820555	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 10, 2024)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 16337994, 27714481, 29979965, 30224644, 12826609, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000820555

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 10, 2024)

germline

clinical testing

PubMed (6)
[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

Mutational analysis of TP53 and p21 in familial and sporadic ovarian cancer in Japan.

Amikura T, Sekine M, Hirai Y, Fujimoto S, Hatae M, Kobayashi I, Fujii T, Nagata I, Ushijima K, Obata K, Suzuki M, Yoshinaga M, Umesaki N, Satoh S, Enomoto T, Motoyama S, Nishino K, Haino K, Tanaka K; Japanese Familial Ovarian Cancer Study Group.

Gynecol Oncol. 2006 Feb;100(2):365-71. Epub 2005 Dec 9.

PubMed [citation]

PMID:: 16337994

TP53 and CDKN1A mutation analysis in families with Li-Fraumeni and Li-Fraumeni like syndromes.

Andrade RC, Dos Santos AC, de Aguirre Neto JC, Nevado J, Lapunzina P, Vargas FR.

Fam Cancer. 2017 Apr;16(2):243-248. doi: 10.1007/s10689-016-9935-z.

PubMed [citation]

PMID:: 27714481

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000820555.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This sequence change replaces isoleucine, which is neutral and non-polar, with asparagine, which is neutral and polar, at codon 195 of the TP53 protein (p.Ile195Asn). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with rhabdomyosarcoma and ovarian cancer (PMID: 16337994, 27714481). ClinVar contains an entry for this variant (Variation ID: 376618). Invitae Evidence Modeling incorporating data from in vitro experimental studies (PMID: 12826609, 29979965, 30224644) indicates that this missense variant is expected to disrupt TP53 function with a positive predictive value of 97.5%. Experimental studies have shown that this missense change affects TP53 function (PMID: 12826609). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of 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: May 16, 2025

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