NM_000546.6(TP53):c.197T>G (p.Met66Arg) AND Li-Fraumeni syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 29, 2022
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:: RCV002297112.4

Allele description [Variation Report for NM_000546.6(TP53):c.197T>G (p.Met66Arg)]

NM_000546.6(TP53):c.197T>G (p.Met66Arg)

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.197T>G (p.Met66Arg)

HGVS:

NC_000017.11:g.7676172A>C
NG_017013.2:g.16379T>G
NM_000546.6:c.197T>GMANE SELECT
NM_001126112.3:c.197T>G
NM_001126113.3:c.197T>G
NM_001126114.3:c.197T>G
NM_001126118.2:c.80T>G
NM_001276695.3:c.80T>G
NM_001276696.3:c.80T>G
NM_001276760.3:c.80T>G
NM_001276761.3:c.80T>G
NM_001407262.1:c.197T>G
NM_001407263.1:c.80T>G
NM_001407264.1:c.197T>G
NM_001407265.1:c.80T>G
NM_001407266.1:c.197T>G
NM_001407267.1:c.80T>G
NM_001407268.1:c.197T>G
NM_001407269.1:c.80T>G
NM_001407270.1:c.197T>G
NM_001407271.1:c.80T>G
NP_000537.3:p.Met66Arg
NP_000537.3:p.Met66Arg
NP_001119584.1:p.Met66Arg
NP_001119584.1:p.Met66Arg
NP_001119585.1:p.Met66Arg
NP_001119585.1:p.Met66Arg
NP_001119586.1:p.Met66Arg
NP_001119586.1:p.Met66Arg
NP_001119590.1:p.Met27Arg
NP_001119590.1:p.Met27Arg
NP_001263624.1:p.Met27Arg
NP_001263625.1:p.Met27Arg
NP_001263689.1:p.Met27Arg
NP_001263690.1:p.Met27Arg
NP_001394191.1:p.Met66Arg
NP_001394192.1:p.Met27Arg
NP_001394193.1:p.Met66Arg
NP_001394194.1:p.Met27Arg
NP_001394195.1:p.Met66Arg
NP_001394196.1:p.Met27Arg
NP_001394197.1:p.Met66Arg
NP_001394198.1:p.Met27Arg
NP_001394199.1:p.Met66Arg
NP_001394200.1:p.Met27Arg
LRG_321t1:c.197T>G
LRG_321t2:c.197T>G
LRG_321t3:c.197T>G
LRG_321t4:c.197T>G
LRG_321t8:c.80T>G
LRG_321:g.16379T>G
LRG_321:p.Met66Arg
LRG_321p1:p.Met66Arg
LRG_321p3:p.Met66Arg
LRG_321p4:p.Met66Arg
LRG_321p8:p.Met27Arg
NC_000017.10:g.7579490A>C
NM_000546.5:c.197T>G
NM_001126112.2:c.197T>G
NM_001126113.2:c.197T>G
NM_001126114.2:c.197T>G
NM_001126118.1:c.80T>G
NR_176326.1:n.339T>G

Protein change:

M27R

Molecular consequence:

NM_000546.6:c.197T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.197T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.197T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.197T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.80T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.80T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.80T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.80T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.80T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407262.1:c.197T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407263.1:c.80T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407264.1:c.197T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407265.1:c.80T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407266.1:c.197T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407267.1:c.80T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407268.1:c.197T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407269.1:c.80T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407270.1:c.197T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407271.1:c.80T>G - 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
SCV002597614	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 29, 2022)	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

SCV002597614

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 29, 2022)

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002597614.3

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

Description

This sequence change replaces methionine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 66 of the TP53 protein (p.Met66Arg). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TP53-related conditions. Advanced modeling of experimental studies (such as gene expression, population dynamics, functional pathways, and cell-cycle effects in cell culture) performed at Invitae indicates that this missense variant is not expected to disrupt TP53 protein function. 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: Nov 10, 2024

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