NM_000546.6(TP53):c.1010G>A (p.Arg337His) AND Li-Fraumeni syndrome 1

Germline classification:: Pathogenic/Likely pathogenic (6 submissions)
Last evaluated:: Jun 18, 2022
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:: RCV000576817.12

Allele description [Variation Report for NM_000546.6(TP53):c.1010G>A (p.Arg337His)]

NM_000546.6(TP53):c.1010G>A (p.Arg337His)

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.1010G>A (p.Arg337His)

HGVS:

NC_000017.11:g.7670699C>T
NG_017013.2:g.21852G>A
NM_000546.6:c.1010G>AMANE SELECT
NM_001126112.3:c.1010G>A
NM_001126113.3:c.*29G>A
NM_001126114.3:c.*117G>A
NM_001126115.2:c.614G>A
NM_001126116.2:c.*117G>A
NM_001126117.2:c.*29G>A
NM_001126118.2:c.893G>A
NM_001276695.3:c.*29G>A
NM_001276696.3:c.*117G>A
NM_001276697.3:c.533G>A
NM_001276698.3:c.*117G>A
NM_001276699.3:c.*29G>A
NM_001276760.3:c.893G>A
NM_001276761.3:c.893G>A
NP_000537.3:p.Arg337His
NP_000537.3:p.Arg337His
NP_001119584.1:p.Arg337His
NP_001119587.1:p.Arg205His
NP_001119590.1:p.Arg298His
NP_001263626.1:p.Arg178His
NP_001263689.1:p.Arg298His
NP_001263690.1:p.Arg298His
LRG_321t1:c.1010G>A
LRG_321:g.21852G>A
LRG_321p1:p.Arg337His
NC_000017.10:g.7574017C>T
NM_000546.4:c.1010G>A
NM_000546.5:c.1010G>A
P04637:p.Arg337His
p.R337H

Protein change:

R178H; ARG337HIS

Links:

UniProtKB: P04637#VAR_035016; OMIM: 191170.0035; dbSNP: rs121912664

NCBI 1000 Genomes Browser:

rs121912664

Molecular consequence:

NM_001126113.3:c.*29G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001126114.3:c.*117G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001126116.2:c.*117G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001126117.2:c.*29G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001276695.3:c.*29G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001276696.3:c.*117G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001276698.3:c.*117G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001276699.3:c.*29G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_000546.6:c.1010G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.1010G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126115.2:c.614G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.893G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276697.3:c.533G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.893G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.893G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Li-Fraumeni syndrome 1 (LFS)
Identifiers:: Gene: 553989; MedGen: C1835398; Orphanet: 524; OMIM: 151623

Recent activity

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PREDICTED: Mus musculus Rho/Rac guanine nucleotide exchange factor 18 (Arhgef18)...
PREDICTED: Mus musculus Rho/Rac guanine nucleotide exchange factor 18 (Arhgef18), transcript variant X1, mRNA
gi|1907186205|ref|XM_030243209.2|

Nucleotide
Mus musculus Fc receptor like 2 (Fcrl2), transcript variant 2, mRNA
Mus musculus Fc receptor like 2 (Fcrl2), transcript variant 2, mRNA
gi|2470813085|ref|NM_030707.4|

Nucleotide
cytochrome oxidase subunit I, partial (mitochondrion) [Orthoptera sp. NZAC 03013...
cytochrome oxidase subunit I, partial (mitochondrion) [Orthoptera sp. NZAC 03013556]
gi|808155983|gb|AKC97320.1|

Protein
PREDICTED: Homo sapiens protein phosphatase, Mg2+/Mn2+ dependent 1K (PPM1K), tra...
PREDICTED: Homo sapiens protein phosphatase, Mg2+/Mn2+ dependent 1K (PPM1K), transcript variant X3, mRNA
gi|2462595169|ref|XM_054349045.1|

Nucleotide
UI-M-BH2.1-apw-g-05-0-UI.s1 NIH_BMAP_M_S3.1 Mus musculus cDNA clone UI-M-BH2.1-a...
UI-M-BH2.1-apw-g-05-0-UI.s1 NIH_BMAP_M_S3.1 Mus musculus cDNA clone UI-M-BH2.1-apw-g-05-0-UI 3', mRNA sequence
gi|6100210|gnl|dbEST|3269982|gb|AW1 .1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000677744	Counsyl	criteria provided, single submitter (Counsyl Autosomal Dominant Disease Classification criteria (2015))	Pathogenic (Feb 16, 2017)	unknown	clinical testing	PubMed (12) [See all records that cite these PMIDs] 21192060, 12826609, 27223487, 16033918, 26452166, 27663983, 26681051, 10864200, 19717094, 11753428, 16494995, 26572807 Citation Link,
SCV002030174	Baylor Genetics - CSER-TexasKidsCanSeq	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 9, 2021)	maternal	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002097308	DASA	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 14, 2022)	germline	clinical testing	PubMed (10) [See all records that cite these PMIDs] 28369373, 20407015, 20301488, 28387921, 28864397, 28984303, 28968711, 28756477, 30107858, 25741868
SCV002582996	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jun 18, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004183390	Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 14, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005382098	Institute of Immunology and Genetics Kaiserslautern	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 21, 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	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	maternal	yes	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

Association of the highly prevalent TP53 R337H mutation with pediatric choroid plexus carcinoma and osteosarcoma in southeast Brazil.

Seidinger AL, Mastellaro MJ, Paschoal Fortes F, Godoy Assumpção J, Aparecida Cardinalli I, Aparecida Ganazza M, Correa Ribeiro R, Brandalise SR, Dos Santos Aguiar S, Yunes JA.

Cancer. 2011 May 15;117(10):2228-35. doi: 10.1002/cncr.25826. Epub 2010 Dec 29.

PubMed [citation]

PMID:: 21192060

Understanding the function-structure and function-mutation relationships of p53 tumor suppressor protein by high-resolution missense mutation analysis.

Kato S, Han SY, Liu W, Otsuka K, Shibata H, Kanamaru R, Ishioka C.

Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8424-9. Epub 2003 Jun 25.

PubMed [citation]

PMID:: 12826609
PMCID:: PMC166245

See all PubMed Citations (22)

Details of each submission

From Counsyl, SCV000677744.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (12)

#	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

From Baylor Genetics - CSER-TexasKidsCanSeq, SCV002030174.1

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

Description

This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	maternal	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From DASA, SCV002097308.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (10)

Description

Well-established in vitro or in vivo functional studies supportive of a damaging effect on the gene or gene product (PMID: 28369373; 20407015) - PS3. The c.1010G>A;p.(Arg337His) missense variant has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 12379; PMID: 20301488; 28387921; 28864397; 28984303; 28968711; 28756477; 30107858) - PS4. The variant is located in a mutational hot spot and/or critical and well-established functional domain (P53_tetramer) - PM1. Pathogenic missense variant in this residue have been reported (ClinVar ID: 142536 - c.1009C>T;p.(Arg337Cys)) - PM5. Multiple lines of computational evidence support a deleterious effect on the gene or gene product - PP3. and allele frequency is greater than expected for disorder - BS1. In summary, the currently available evidence indicates that the variant is pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

From Genome-Nilou Lab, SCV002582996.1

#	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 Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein, SCV004183390.1

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

Description

ACMG classification criteria: PS3, PS4, PP1

#	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

From Institute of Immunology and Genetics Kaiserslautern, SCV005382098.1

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

Description

ACMG Criteria: PS3, PM2, PM5, PP3, PP5; Variant was found in heterozygous state.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 3, 2024

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