NM_000546.6(TP53):c.584T>C (p.Ile195Thr) AND Li-Fraumeni syndrome 1

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Feb 15, 2024
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:: RCV002288812.5

Allele description [Variation Report for NM_000546.6(TP53):c.584T>C (p.Ile195Thr)]

NM_000546.6(TP53):c.584T>C (p.Ile195Thr)

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>C (p.Ile195Thr)

HGVS:

NC_000017.11:g.7674947A>G
NG_017013.2:g.17604T>C
NM_000546.6:c.584T>CMANE SELECT
NM_001126112.3:c.584T>C
NM_001126113.3:c.584T>C
NM_001126114.3:c.584T>C
NM_001126115.2:c.188T>C
NM_001126116.2:c.188T>C
NM_001126117.2:c.188T>C
NM_001126118.2:c.467T>C
NM_001276695.3:c.467T>C
NM_001276696.3:c.467T>C
NM_001276697.3:c.107T>C
NM_001276698.3:c.107T>C
NM_001276699.3:c.107T>C
NM_001276760.3:c.467T>C
NM_001276761.3:c.467T>C
NP_000537.3:p.Ile195Thr
NP_000537.3:p.Ile195Thr
NP_001119584.1:p.Ile195Thr
NP_001119585.1:p.Ile195Thr
NP_001119586.1:p.Ile195Thr
NP_001119587.1:p.Ile63Thr
NP_001119588.1:p.Ile63Thr
NP_001119589.1:p.Ile63Thr
NP_001119590.1:p.Ile156Thr
NP_001263624.1:p.Ile156Thr
NP_001263625.1:p.Ile156Thr
NP_001263626.1:p.Ile36Thr
NP_001263627.1:p.Ile36Thr
NP_001263628.1:p.Ile36Thr
NP_001263689.1:p.Ile156Thr
NP_001263690.1:p.Ile156Thr
LRG_321t1:c.584T>C
LRG_321:g.17604T>C
LRG_321p1:p.Ile195Thr
NC_000017.10:g.7578265A>G
NM_000546.4:c.584T>C
NM_000546.5:c.584T>C
P04637:p.Ile195Thr

Protein change:

I156T

Links:

UniProtKB: P04637#VAR_005951; dbSNP: rs760043106

NCBI 1000 Genomes Browser:

rs760043106

Molecular consequence:

NM_000546.6:c.584T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.584T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.584T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.584T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126115.2:c.188T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126116.2:c.188T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126117.2:c.188T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.467T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.467T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.467T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276697.3:c.107T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276698.3:c.107T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276699.3:c.107T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.467T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.467T>C - 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
SCV002583147	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jun 18, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004932961	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Pathogenic (Feb 15, 2024)	unknown	clinical testing	PubMed (4) [See all records that cite these PMIDs] 19930417, 27501770, 19405127, 29979965 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002583147

Genome-Nilou Lab

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jun 18, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV004932961

Myriad Genetics, Inc.

criteria provided, single submitter

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

Pathogenic
(Feb 15, 2024)

unknown

clinical testing

PubMed (4)
[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	no	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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Beyond BRCA1 and BRCA2 wild-type breast and/or ovarian cancer families: germline mutations in TP53 and PTEN.

Blanco A, Graña B, Fachal L, Santamariña M, Cameselle-Teijeiro J, Ruíz-Ponte C, Carracedo A, Vega A.

Clin Genet. 2010 Feb;77(2):193-6. doi: 10.1111/j.1399-0004.2009.01309.x. Epub 2009 Nov 23. No abstract available.

PubMed [citation]

PMID:: 19930417

See all PubMed Citations (5)

Details of each submission

From Genome-Nilou Lab, SCV002583147.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Myriad Genetics, Inc., SCV004932961.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This variant is considered pathogenic. This variant has been reported in multiple individuals with clinical features of gene-specific disease [PMID: 19405127, 19930417, 27501770]. Functional studies indicate this variant impacts protein function [PMID: 19405127, 29979965]. This variant is expected to disrupt protein structure [Myriad internal data].

#	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: Oct 8, 2024

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