NM_005228.5(EGFR):c.2369C>T (p.Thr790Met) AND Lung cancer

Germline classification:: Pathogenic (1 submission)
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:: RCV001823098.12

Allele description [Variation Report for NM_005228.5(EGFR):c.2369C>T (p.Thr790Met)]

NM_005228.5(EGFR):c.2369C>T (p.Thr790Met)

Genes:

EGFR-AS1:EGFR antisense RNA 1 [Gene - HGNC]
EGFR:epidermal growth factor receptor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p11.2

Genomic location:

Preferred name:

NM_005228.5(EGFR):c.2369C>T (p.Thr790Met)

HGVS:

NC_000007.14:g.55181378C>T
NG_007726.3:g.167347C>T
NM_001346897.2:c.2234C>T
NM_001346898.2:c.2369C>T
NM_001346899.2:c.2234C>T
NM_001346900.2:c.2210C>T
NM_001346941.2:c.1568C>T
NM_005228.5:c.2369C>TMANE SELECT
NP_001333826.1:p.Thr745Met
NP_001333827.1:p.Thr790Met
NP_001333828.1:p.Thr745Met
NP_001333829.1:p.Thr737Met
NP_001333870.1:p.Thr523Met
NP_005219.2:p.Thr790Met
LRG_304t1:c.2369C>T
LRG_304:g.167347C>T
NC_000007.13:g.55249071C>T
NM_005228.3:c.2369C>T
NM_005228.4:c.2369C>T
NM_005228.4:c.[2369C>T]
NR_047551.1:n.1193G>A
P00533:p.Thr790Met

Protein change:

T523M; THR790MET

Links:

PharmGKB: 981475450; PharmGKB: 981475450PA131301952; PharmGKB: 981475450PA134687924; PharmGKB Clinical Annotation: 981475450; UniProtKB: P00533#VAR_026098; OMIM: 131550.0006; dbSNP: rs121434569

NCBI 1000 Genomes Browser:

rs121434569

Molecular consequence:

NM_001346897.2:c.2234C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001346898.2:c.2369C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001346899.2:c.2234C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001346900.2:c.2210C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001346941.2:c.1568C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_005228.5:c.2369C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_047551.1:n.1193G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Lung cancer
Synonyms:: Lung cancer, somatic; Malignant tumor of lung
Identifiers:: MONDO: MONDO:0008903; MedGen: C0242379; OMIM: 211980

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PREDICTED: Bubalus bubalis ORMDL sphingolipid biosynthesis regulator 1 (ORMDL1), transcript variant X1, mRNA
gi|2128245725|ref|XM_006076951.3|

Nucleotide
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Cluster Headache
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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002073070	Neuberg Centre For Genomic Medicine, NCGM	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002073070

Neuberg Centre For Genomic Medicine, NCGM

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic

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	not provided	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

Details of each submission

From Neuberg Centre For Genomic Medicine, NCGM, SCV002073070.1

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

Description

The missense variant p.T790M in EGFR (NM_005228.5) has been reported in multiple patients with adenocarcinoma of lung. In majority of the cases the mutation has been detected by somatic testing. Germline mutation T790M has been reported in a subset of patients both with and without disease implying incomplete penetrance (Helena Yu A et al, 2014; Gazdar A et al, 2014; Oxnard GR et al, 2012; Tibaldi C et al, 2011). The variant has been classified by the expert review panel in Clin Var as Pathogenic with respect to drug response. It is present in 10 alleles in heterozygote state (0.003%) in the gnomAD database. There is a moderate physicochemical difference between threonine and methionine. The p.T790M missense variant is predicted to be damaging by both SIFT and PolyPhen2. The nucleotide c.2369 in EGFR is predicted conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as 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		not provided	not provided	not provided	not provided

Last Updated: Nov 3, 2024

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