NM_000546.6(TP53):c.841G>C (p.Asp281His) AND Diffuse midline glioma, H3 K27M-mutant

Germline classification:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of clinical impact:: Tier I - Diagnostic - supports diagnosis (1 submission)
Last evaluated:: Nov 9, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV006254030.1

Allele description [Variation Report for NM_000546.6(TP53):c.841G>C (p.Asp281His)]

NM_000546.6(TP53):c.841G>C (p.Asp281His)

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.841G>C (p.Asp281His)

HGVS:

NC_000017.11:g.7673779C>G
NG_017013.2:g.18772G>C
NM_000546.6:c.841G>CMANE SELECT
NM_001126112.3:c.841G>C
NM_001126113.3:c.841G>C
NM_001126114.3:c.841G>C
NM_001126115.2:c.445G>C
NM_001126116.2:c.445G>C
NM_001126117.2:c.445G>C
NM_001126118.2:c.724G>C
NM_001276695.3:c.724G>C
NM_001276696.3:c.724G>C
NM_001276697.3:c.364G>C
NM_001276698.3:c.364G>C
NM_001276699.3:c.364G>C
NM_001276760.3:c.724G>C
NM_001276761.3:c.724G>C
NP_000537.3:p.Asp281His
NP_001119584.1:p.Asp281His
NP_001119585.1:p.Asp281His
NP_001119586.1:p.Asp281His
NP_001119587.1:p.Asp149His
NP_001119588.1:p.Asp149His
NP_001119589.1:p.Asp149His
NP_001119590.1:p.Asp242His
NP_001263624.1:p.Asp242His
NP_001263625.1:p.Asp242His
NP_001263626.1:p.Asp122His
NP_001263627.1:p.Asp122His
NP_001263628.1:p.Asp122His
NP_001263689.1:p.Asp242His
NP_001263690.1:p.Asp242His
LRG_321:g.18772G>C
NC_000017.10:g.7577097C>G
NM_000546.4:c.841G>C

Protein change:

D122H

Links:

dbSNP: rs764146326

Molecular consequence:

NM_000546.6:c.841G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.841G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.841G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.841G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126115.2:c.445G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126116.2:c.445G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126117.2:c.445G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.724G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.724G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.724G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276697.3:c.364G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276698.3:c.364G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276699.3:c.364G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.724G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.724G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Diffuse midline glioma, H3 K27M-mutant
Identifiers:: MONDO: MONDO:0957196; MedGen: C4289688

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV007104435	Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital	criteria provided, single submitter (AMP/ASCO/CAP Guidelines, 2017)	Tier I - Strong - diagnostic, supports diagnosis (Nov 9, 2022)	somatic	clinical testing	PubMed (9) [See all records that cite these PMIDs] 12826609, 30224644, 29979965, 24705251, 28966033, 22661320, 34796414, 33433639, 27993330

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV007104435

Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital

criteria provided, single submitter

(AMP/ASCO/CAP Guidelines, 2017)

Tier I - Strong - diagnostic, supports diagnosis
(Nov 9, 2022)

somatic

clinical testing

PubMed (9)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method

Citations

PubMed

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

Mutational processes shape the landscape of TP53 mutations in human cancer.

Giacomelli AO, Yang X, Lintner RE, McFarland JM, Duby M, Kim J, Howard TP, Takeda DY, Ly SH, Kim E, Gannon HS, Hurhula B, Sharpe T, Goodale A, Fritchman B, Steelman S, Vazquez F, Tsherniak A, Aguirre AJ, Doench JG, Piccioni F, Roberts CWM, et al.

Nat Genet. 2018 Oct;50(10):1381-1387. doi: 10.1038/s41588-018-0204-y. Epub 2018 Sep 17.

PubMed [citation]

PMID:: 30224644
PMCID:: PMC6168352

See all PubMed Citations (9)

Details of each submission

From Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital, SCV007104435.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (9)

Description

Variant has Tier I (strong) clinical significance as a diagnostic inclusion criterion in diffuse midline glioma, H3 K27M-mutant, based on the following evidence: 1) Documented in one or more cancer databases (e.g., St. Jude Pecan, COSMIC, CIViC, OncoKB). 2) Appears in one or more well-established professional guidelines (e.g., World Health Organization [WHO]; National Comprehensive Cancer Network [NCCN]) as providing diagnostic, prognostic, or therapeutic information. 3) Information in the literature supports potential biologic effect of variant (PMIDs: 12826609, 30224644, 29979965). 4) Diagnostic for a specific tumor type/classification based on well-powered studies with expert-level consensus (Evidence Level B; PMIDs: 24705251, 28966033, 22661320, 34796414, 33433639).

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

Last Updated: Apr 12, 2026

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