NM_000546.6(TP53):c.637C>T (p.Arg213Ter) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Oct 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:: RCV000213050.15

Allele description [Variation Report for NM_000546.6(TP53):c.637C>T (p.Arg213Ter)]

NM_000546.6(TP53):c.637C>T (p.Arg213Ter)

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>T (p.Arg213Ter)

Other names:

p.R213*:CGA>TGA

HGVS:

NC_000017.11:g.7674894G>A
NG_017013.2:g.17657C>T
NM_000546.6:c.637C>TMANE SELECT
NM_001126112.3:c.637C>T
NM_001126113.3:c.637C>T
NM_001126114.3:c.637C>T
NM_001126115.2:c.241C>T
NM_001126116.2:c.241C>T
NM_001126117.2:c.241C>T
NM_001126118.2:c.520C>T
NM_001276695.3:c.520C>T
NM_001276696.3:c.520C>T
NM_001276697.3:c.160C>T
NM_001276698.3:c.160C>T
NM_001276699.3:c.160C>T
NM_001276760.3:c.520C>T
NM_001276761.3:c.520C>T
NP_000537.3:p.Arg213Ter
NP_000537.3:p.Arg213Ter
NP_001119584.1:p.Arg213Ter
NP_001119585.1:p.Arg213Ter
NP_001119586.1:p.Arg213Ter
NP_001119587.1:p.Arg81Ter
NP_001119588.1:p.Arg81Ter
NP_001119589.1:p.Arg81Ter
NP_001119590.1:p.Arg174Ter
NP_001119590.1:p.Arg174Ter
NP_001263624.1:p.Arg174Ter
NP_001263625.1:p.Arg174Ter
NP_001263626.1:p.Arg54Ter
NP_001263627.1:p.Arg54Ter
NP_001263628.1:p.Arg54Ter
NP_001263689.1:p.Arg174Ter
NP_001263690.1:p.Arg174Ter
LRG_321t1:c.637C>T
LRG_321t8:c.520C>T
LRG_321:g.17657C>T
LRG_321p1:p.Arg213Ter
LRG_321p8:p.Arg174Ter
NC_000017.10:g.7578212G>A
NM_000546.4:c.637C>T
NM_000546.5:c.637C>T
NM_001126118.1:c.520C>T
NM_001276696.1:c.520C>T
c.637C>T
p.Arg213Stop
p.Arg213X
p.R213*

Protein change:

R174*

Links:

dbSNP: rs397516436

NCBI 1000 Genomes Browser:

rs397516436

Molecular consequence:

NM_000546.6:c.637C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001126112.3:c.637C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001126113.3:c.637C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001126114.3:c.637C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001126115.2:c.241C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001126116.2:c.241C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001126117.2:c.241C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001126118.2:c.520C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001276695.3:c.520C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001276696.3:c.520C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001276697.3:c.160C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001276698.3:c.160C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001276699.3:c.160C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001276760.3:c.520C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001276761.3:c.520C>T - nonsense - [Sequence Ontology: SO:0001587]

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
SCV000149639	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Jun 17, 2021)	germline	clinical testing	Citation Link,
SCV004221368	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Pathogenic (Oct 18, 2022)	unknown	clinical testing	PubMed (12) [See all records that cite these PMIDs] 32000721, 29753700, 29489754, 28503720, 27146902, 27059324, 26681312, 26425688, 32994724, 31278746, 21552135, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000149639

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Jun 17, 2021)

germline

clinical testing

Citation Link,

SCV004221368

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Pathogenic
(Oct 18, 2022)

unknown

clinical testing

PubMed (12)
[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	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

Pattern of nucleotide variants of TP53 and their correlation with the expression of p53 and its downstream proteins in a Sri Lankan cohort of breast and colorectal cancer patients.

Manoharan V, Karunanayake EH, Tennekoon KH, De Silva S, Imthikab AIA, De Silva K, Angunawela P, Vishwakula S, Lunec J.

BMC Cancer. 2020 Jan 30;20(1):72. doi: 10.1186/s12885-020-6573-5.

PubMed [citation]

PMID:: 32000721
PMCID:: PMC6990524

Spectrum and prevalence of genetic predisposition in medulloblastoma: a retrospective genetic study and prospective validation in a clinical trial cohort.

Waszak SM, Northcott PA, Buchhalter I, Robinson GW, Sutter C, Groebner S, Grund KB, Brugières L, Jones DTW, Pajtler KW, Morrissy AS, Kool M, Sturm D, Chavez L, Ernst A, Brabetz S, Hain M, Zichner T, Segura-Wang M, Weischenfeldt J, Rausch T, Mardin BR, et al.

Lancet Oncol. 2018 Jun;19(6):785-798. doi: 10.1016/S1470-2045(18)30242-0. Epub 2018 May 9.

PubMed [citation]

PMID:: 29753700
PMCID:: PMC5984248

See all PubMed Citations (12)

Details of each submission

From GeneDx, SCV000149639.14

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

Description

Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Published functional studies demonstrate a damaging effect: loss of DNA binding and growth suppression activities (Malcikova 2010, Kotler 2018); Not observed at significant frequency in large population cohorts (Lek 2016); This variant is associated with the following publications: (PMID: 11479205, 25525159, 15656799, 24803582, 30309854, 10486318, 28056804, 29655027, 27059324, 29489754, 20128691, 8134126, 21552135, 20658636, 21626334, 22203015, 15099937, 7887414, 16401470, 24220311, 23334668, 24702488, 26681312, 15902285, 28503720, 29351612, 29979965, 30412573, 29354595, 29700339, 29076966, 21225465, 27146902, 26425688, 9667734, 20522432, 29753700, 30720243, 31278746, 27535533, 31105275, 32000721, 30816478)

#	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 Quest Diagnostics Nichols Institute San Juan Capistrano, SCV004221368.1

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

Description

This nonsense variant causes the premature termination of TP53 protein synthesis. It has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). In the published literature, the variant has been reported in individuals with Li Fraumeni Syndrome (PMID: 21552135 (2011)), colorectal cancer (PMID: 26425688 (2015), 32000721 (2020)), breast cancer (PMID: 32994724 (2020), 28503720 (2017), 26681312 (2015)), and ovarian cancer (PMID: 27059324 (2016)). The variant has also been reported in individuals with glioma (PMID: 31278746 (2019)) and medulloblastoma (PMID: 29753700 (2018), 29489754 (2018). Based on the available information, this variant is classified as pathogenic.

#	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

Last Updated: Aug 25, 2024

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