NM_000546.6(TP53):c.584T>G (p.Ile195Ser) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 3, 2019
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:: RCV001184465.4

Allele description [Variation Report for NM_000546.6(TP53):c.584T>G (p.Ile195Ser)]

NM_000546.6(TP53):c.584T>G (p.Ile195Ser)

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>G (p.Ile195Ser)

HGVS:

NC_000017.11:g.7674947A>C
NG_017013.2:g.17604T>G
NM_000546.6:c.584T>GMANE SELECT
NM_001126112.3:c.584T>G
NM_001126113.3:c.584T>G
NM_001126114.3:c.584T>G
NM_001126115.2:c.188T>G
NM_001126116.2:c.188T>G
NM_001126117.2:c.188T>G
NM_001126118.2:c.467T>G
NM_001276695.3:c.467T>G
NM_001276696.3:c.467T>G
NM_001276697.3:c.107T>G
NM_001276698.3:c.107T>G
NM_001276699.3:c.107T>G
NM_001276760.3:c.467T>G
NM_001276761.3:c.467T>G
NP_000537.3:p.Ile195Ser
NP_000537.3:p.Ile195Ser
NP_001119584.1:p.Ile195Ser
NP_001119585.1:p.Ile195Ser
NP_001119586.1:p.Ile195Ser
NP_001119587.1:p.Ile63Ser
NP_001119588.1:p.Ile63Ser
NP_001119589.1:p.Ile63Ser
NP_001119590.1:p.Ile156Ser
NP_001263624.1:p.Ile156Ser
NP_001263625.1:p.Ile156Ser
NP_001263626.1:p.Ile36Ser
NP_001263627.1:p.Ile36Ser
NP_001263628.1:p.Ile36Ser
NP_001263689.1:p.Ile156Ser
NP_001263690.1:p.Ile156Ser
LRG_321t1:c.584T>G
LRG_321:g.17604T>G
LRG_321p1:p.Ile195Ser
NC_000017.10:g.7578265A>C
NM_000546.5:c.584T>G

Protein change:

I156S

Links:

dbSNP: rs760043106

NCBI 1000 Genomes Browser:

rs760043106

Molecular consequence:

NM_000546.6:c.584T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.584T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.584T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.584T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126115.2:c.188T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126116.2:c.188T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126117.2:c.188T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.467T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.467T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.467T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276697.3:c.107T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276698.3:c.107T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276699.3:c.107T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.467T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.467T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001350433	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Sep 3, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001350433

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Sep 3, 2019)

germline

clinical testing

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

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

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

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV001350433.2

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

Description

This missense variant replaces isoleucine with serine at codon 195 of the TP53 protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on protein structure and function. A different variant affecting the same codon, c.584T>C (p.Ile195Thr), is considered to be disease-causing (ClinVar variation ID: 216077), suggesting that isoleucine or similar amino acid at this position is important for the protein function. Splice site prediction tools suggest that this variant may not impact RNA splicing. Functional studies have shown that this variant to be non-functional in yeast transcription activation assays and in a cell proliferation assay in p53-null mammalian cells (PMID: 12826609, 23897043, 29979965). To our knowledge, this variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Although there is a suspicion that this variant may be associated with disease, clinical evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is 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: Sep 16, 2024

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