NM_000546.6(TP53):c.638G>A (p.Arg213Gln) AND not provided

Germline classification:: Pathogenic (5 submissions)
Last evaluated:: Nov 16, 2021
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:: RCV000420734.14

Allele description [Variation Report for NM_000546.6(TP53):c.638G>A (p.Arg213Gln)]

NM_000546.6(TP53):c.638G>A (p.Arg213Gln)

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.638G>A (p.Arg213Gln)

HGVS:

NC_000017.11:g.7674893C>T
NG_017013.2:g.17658G>A
NM_000546.6:c.638G>AMANE SELECT
NM_001126112.3:c.638G>A
NM_001126113.3:c.638G>A
NM_001126114.3:c.638G>A
NM_001126115.2:c.242G>A
NM_001126116.2:c.242G>A
NM_001126117.2:c.242G>A
NM_001126118.2:c.521G>A
NM_001276695.3:c.521G>A
NM_001276696.3:c.521G>A
NM_001276697.3:c.161G>A
NM_001276698.3:c.161G>A
NM_001276699.3:c.161G>A
NM_001276760.3:c.521G>A
NM_001276761.3:c.521G>A
NP_000537.3:p.Arg213Gln
NP_000537.3:p.Arg213Gln
NP_001119584.1:p.Arg213Gln
NP_001119585.1:p.Arg213Gln
NP_001119586.1:p.Arg213Gln
NP_001119587.1:p.Arg81Gln
NP_001119588.1:p.Arg81Gln
NP_001119589.1:p.Arg81Gln
NP_001119590.1:p.Arg174Gln
NP_001263624.1:p.Arg174Gln
NP_001263625.1:p.Arg174Gln
NP_001263626.1:p.Arg54Gln
NP_001263627.1:p.Arg54Gln
NP_001263628.1:p.Arg54Gln
NP_001263689.1:p.Arg174Gln
NP_001263690.1:p.Arg174Gln
LRG_321t1:c.638G>A
LRG_321:g.17658G>A
LRG_321p1:p.Arg213Gln
NC_000017.10:g.7578211C>T
NM_000546.4:c.638G>A
NM_000546.5:c.638G>A
P04637:p.Arg213Gln
p.R213Q

Protein change:

R174Q

Links:

UniProtKB: P04637#VAR_005955; dbSNP: rs587778720

NCBI 1000 Genomes Browser:

rs587778720

Molecular consequence:

NM_000546.6:c.638G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.638G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.638G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.638G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126115.2:c.242G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126116.2:c.242G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126117.2:c.242G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.521G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.521G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.521G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276697.3:c.161G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276698.3:c.161G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276699.3:c.161G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.521G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.521G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000517027	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Nov 16, 2021)	germline	clinical testing	Citation Link,
SCV001449717	Clinical Genetics and Genomics, Karolinska University Hospital	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 27, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001469324	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Pathogenic (Jan 13, 2020)	unknown	clinical testing	PubMed (7) [See all records that cite these PMIDs] 26270727, 24728327, 23259501, 30299350, 16736287, 30720243, 26467025
SCV001905965	Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV001953963	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Pathogenic	germline	clinical testing

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	1	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

Clinical Actionability of Multigene Panel Testing for Hereditary Breast and Ovarian Cancer Risk Assessment.

Desmond A, Kurian AW, Gabree M, Mills MA, Anderson MJ, Kobayashi Y, Horick N, Yang S, Shannon KM, Tung N, Ford JM, Lincoln SE, Ellisen LW.

JAMA Oncol. 2015 Oct;1(7):943-51. doi: 10.1001/jamaoncol.2015.2690.

PubMed [citation]

PMID:: 26270727

See all PubMed Citations (8)

Details of each submission

From GeneDx, SCV000517027.7

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

Description

Published functional studies demonstrate a damaging effect: partial to non-functional transactivation activity, deficient in targeting the consensus binding sequencing of p53 in the regulatory region of the p21 gene, resulting in an inability to up-regulate cell cycle arrest and apoptosis (Pan 2000, Kato 2003, Monti 2011, Zhang 2014, Kotler 2018); Not observed at significant frequency in large population cohorts (Lek 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; In-silico analysis is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 25268584, 16494995, 29979965, 28472496, 30224644, 28643165, 29058986, 25925845, 10871862, 14583457, 23259501, 16736287, 19468865, 8080050, 24728327, 1915267, 8492087, 21343334, 17606709, 24384472, 26270727, 26829319, 20522432, 28369373, 29076966, 18208484, 28861920, 29489754, 28724667, 30455982, 30675318, 30299350, 30720243, 30840781, 31119730, 30577483, 31481248, 31105275, 31447099, 33138793, 33818021, 17541742, 15510160)

#	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

From Clinical Genetics and Genomics, Karolinska University Hospital, SCV001449717.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	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	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV001469324.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

The best available variant frequency is uninformative because there are too few occurrences in population data. Found in at least one patient with expected phenotype for this gene. Predicted to have a damaging effect on the protein. Located in potentially critical domain of the protein. Two other pathogenic or likely pathogenic variants affect the same amino acid. Assessment of experimental evidence suggests this variant results in abnormal protein function. Inconclusive segregation with disease

#	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 Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute - VKGL Data-share Consensus, SCV001905965.1

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

#	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

From Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus, SCV001953963.1

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

#	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: May 12, 2024

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