NM_000546.6(TP53):c.637C>G (p.Arg213Gly) AND Li-Fraumeni syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 24, 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:: RCV002524699.3

Allele description [Variation Report for NM_000546.6(TP53):c.637C>G (p.Arg213Gly)]

NM_000546.6(TP53):c.637C>G (p.Arg213Gly)

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.637C>G (p.Arg213Gly)

HGVS:

NC_000017.11:g.7674894G>C
NG_017013.2:g.17657C>G
NM_000546.6:c.637C>GMANE SELECT
NM_001126112.3:c.637C>G
NM_001126113.3:c.637C>G
NM_001126114.3:c.637C>G
NM_001126115.2:c.241C>G
NM_001126116.2:c.241C>G
NM_001126117.2:c.241C>G
NM_001126118.2:c.520C>G
NM_001276695.3:c.520C>G
NM_001276696.3:c.520C>G
NM_001276697.3:c.160C>G
NM_001276698.3:c.160C>G
NM_001276699.3:c.160C>G
NM_001276760.3:c.520C>G
NM_001276761.3:c.520C>G
NP_000537.3:p.Arg213Gly
NP_001119584.1:p.Arg213Gly
NP_001119585.1:p.Arg213Gly
NP_001119586.1:p.Arg213Gly
NP_001119587.1:p.Arg81Gly
NP_001119588.1:p.Arg81Gly
NP_001119589.1:p.Arg81Gly
NP_001119590.1:p.Arg174Gly
NP_001263624.1:p.Arg174Gly
NP_001263625.1:p.Arg174Gly
NP_001263626.1:p.Arg54Gly
NP_001263627.1:p.Arg54Gly
NP_001263628.1:p.Arg54Gly
NP_001263689.1:p.Arg174Gly
NP_001263690.1:p.Arg174Gly
LRG_321:g.17657C>G
NC_000017.10:g.7578212G>C
NM_000546.4:c.637C>G

Protein change:

R174G

Links:

dbSNP: rs397516436

NCBI 1000 Genomes Browser:

rs397516436

Molecular consequence:

NM_000546.6:c.637C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.637C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.637C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.637C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126115.2:c.241C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126116.2:c.241C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126117.2:c.241C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.520C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.520C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.520C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276697.3:c.160C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276698.3:c.160C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276699.3:c.160C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.520C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.520C>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
SCV003317130	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 24, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 33332384, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003317130

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 24, 2022)

germline

clinical testing

PubMed (2)
[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

Nationwide germline whole genome sequencing of 198 consecutive pediatric cancer patients reveals a high incidence of cancer prone syndromes.

Byrjalsen A, Hansen TVO, Stoltze UK, Mehrjouy MM, Barnkob NM, Hjalgrim LL, Mathiasen R, Lautrup CK, Gregersen PA, Hasle H, Wehner PS, Tuckuviene R, Sackett PW, Laspiur AO, Rossing M, Marvig RL, Tommerup N, Olsen TE, Scheie D, Gupta R, Gerdes AM, Schmiegelow K, et al.

PLoS Genet. 2020 Dec;16(12):e1009231. doi: 10.1371/journal.pgen.1009231.

PubMed [citation]

PMID:: 33332384
PMCID:: PMC7787686

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 Invitae, SCV003317130.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 213 of the TP53 protein (p.Arg213Gly). This variant is not present in population databases (gnomAD no frequency). 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. 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 expected to disrupt TP53 protein function. ClinVar contains an entry for this variant (Variation ID: 376651). This missense change has been observed in individual(s) with precursor B-cell acute lymphoblastic leukemia (PMID: 33332384).

#	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 12, 2024

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