NM_005228.5(EGFR):c.2573T>G (p.Leu858Arg) AND Non-small cell lung carcinoma

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 14, 2015
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of clinical impact:: Tier I - Therapeutic - sensitivity/response (2 submissions)
Last evaluated:: Feb 23, 2018
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:: RCV000435684.11

Allele description [Variation Report for NM_005228.5(EGFR):c.2573T>G (p.Leu858Arg)]

NM_005228.5(EGFR):c.2573T>G (p.Leu858Arg)

Gene:

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.2573T>G (p.Leu858Arg)

HGVS:

NC_000007.14:g.55191822T>G
NG_007726.3:g.177791T>G
NM_001346897.2:c.2438T>G
NM_001346898.2:c.2573T>G
NM_001346899.2:c.2438T>G
NM_001346900.2:c.2414T>G
NM_001346941.2:c.1772T>G
NM_005228.5:c.2573T>GMANE SELECT
NP_001333826.1:p.Leu813Arg
NP_001333827.1:p.Leu858Arg
NP_001333828.1:p.Leu813Arg
NP_001333829.1:p.Leu805Arg
NP_001333870.1:p.Leu591Arg
NP_005219.2:p.Leu858Arg
LRG_304t1:c.2573T>G
LRG_304:g.177791T>G
NC_000007.13:g.55259515T>G
NM_005228.3:c.2573T>G
P00533:p.Leu858Arg

Protein change:

L591R; LEU858ARG

Links:

PharmGKB: 981420042; PharmGKB: 981420042PA131301952; PharmGKB: 981475838; PharmGKB: 981475838PA134687924; PharmGKB: 981475880; PharmGKB Clinical Annotation: 981420042; PharmGKB Clinical Annotation: 981475838; PharmGKB Clinical Annotation: 981475880; UniProtKB: P00533#VAR_019298; OMIM: 131550.0002; dbSNP: rs121434568

NCBI 1000 Genomes Browser:

rs121434568

Molecular consequence:

NM_001346897.2:c.2438T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001346898.2:c.2573T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001346899.2:c.2438T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001346900.2:c.2414T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001346941.2:c.1772T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_005228.5:c.2573T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Non-small cell lung carcinoma (NSCLC)
Synonyms:: Non-small cell lung cancer
Identifiers:: MONDO: MONDO:0005233; MeSH: D002289; MedGen: C0007131; Human Phenotype Ontology: HP:0030358

Recent activity

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txid1352[orgn] AND "isolate E31902 2016"[All Fields] (1)
SRA
LOC128966642 [Homo sapiens]
LOC128966642 [Homo sapiens]
Gene ID:128966642

Gene
TPA_asm: Enterococcus faecium strain VREN0116, whole genome shotgun sequencing p...
TPA_asm: Enterococcus faecium strain VREN0116, whole genome shotgun sequencing project
gi|2027317768|tpg|DADXYK000000000.1 YK010000000

Nucleotide
FAS Fas cell surface death receptor [Homo sapiens]
FAS Fas cell surface death receptor [Homo sapiens]
Gene ID:355

Gene
Gene Links for GEO Profiles (Select 125861371) (1)
Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000504239	Database of Curated Mutations (DoCM)	no assertion criteria provided	Pathogenic (Jul 14, 2015)	somatic	literature only	PubMed (22) [See all records that cite these PMIDs] 15118125, 19692680, 20022809, 23102728, 23948351, 21783417, 20573926, 15329413, 22753918, 21670455, 19922469, 23816960, 19096302, 16204070, 19692684, 15118073, 22452895, 22285168, 20479403, 25157968, 19455431, 18303429 Citation Link,
SCV004565358	CIViC knowledgebase, Washington University School of Medicine	criteria provided, single submitter (AMP/ASCO/CAP Guidelines, 2017)	Tier I - Strong - therapeutic, sensitivity/response (Feb 23, 2018)	somatic	curation	PubMed (9) [See all records that cite these PMIDs] 24736073, 22285168, 27032107, 19147750, 17877814, 21132006, 27102076, 24868098, 27993330 Citation Link,
SCV004565359	CIViC knowledgebase, Washington University School of Medicine	criteria provided, single submitter (AMP/ASCO/CAP Guidelines, 2017)	Tier I - Strong - therapeutic, sensitivity/response (Feb 22, 2018)	somatic	curation	PubMed (7) [See all records that cite these PMIDs] 23982599, 18408761, 24439929, 26515464, 22452895, 23816960, 27993330 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000504239

Database of Curated Mutations (DoCM)

no assertion criteria provided

Pathogenic
(Jul 14, 2015)

somatic

literature only

PubMed (22)
[See all records that cite these PMIDs]

Citation Link,

SCV004565358

CIViC knowledgebase, Washington University School of Medicine

criteria provided, single submitter

(AMP/ASCO/CAP Guidelines, 2017)

Tier I - Strong - therapeutic, sensitivity/response
(Feb 23, 2018)

somatic

curation

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

Citation Link,

SCV004565359

CIViC knowledgebase, Washington University School of Medicine

criteria provided, single submitter

(AMP/ASCO/CAP Guidelines, 2017)

Tier I - Strong - therapeutic, sensitivity/response
(Feb 22, 2018)

somatic

curation

PubMed (7)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	somatic	yes	not provided	not provided	not provided	not provided	not provided	literature only, curation

Citations

PubMed

EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy.

Paez JG, Jänne PA, Lee JC, Tracy S, Greulich H, Gabriel S, Herman P, Kaye FJ, Lindeman N, Boggon TJ, Naoki K, Sasaki H, Fujii Y, Eck MJ, Sellers WR, Johnson BE, Meyerson M.

Science. 2004 Jun 4;304(5676):1497-500. Epub 2004 Apr 29.

PubMed [citation]

PMID:: 15118125

Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma.

Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, Sunpaweravong P, Han B, Margono B, Ichinose Y, Nishiwaki Y, Ohe Y, Yang JJ, Chewaskulyong B, Jiang H, Duffield EL, Watkins CL, Armour AA, Fukuoka M.

N Engl J Med. 2009 Sep 3;361(10):947-57. doi: 10.1056/NEJMoa0810699. Epub 2009 Aug 19.

PubMed [citation]

PMID:: 19692680

See all PubMed Citations (34)

Details of each submission

From Database of Curated Mutations (DoCM), SCV000504239.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (22)

#	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

From CIViC knowledgebase, Washington University School of Medicine, SCV004565358.1

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

Description

L858R is among the most common sensitizing EGFR mutations in NSCLC, and is assessed via DNA mutational analysis including Sanger sequencing and next generation sequencing methods. Tyrosine kinase inhibitor erlotinib is associated with improved progression free survival over chemotherapy in EGFR L858R patients (civic.EID:885).

#	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

From CIViC knowledgebase, Washington University School of Medicine, SCV004565359.1

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

Description

L858R is among the most common sensitizing EGFR mutations in NSCLC, and is assessed via DNA mutational analysis, including Sanger sequencing and next generation sequencing methods. Tyrosine kinase inhibitor afatinib is FDA approved as a first line systemic therapy in NSCLC with sensitizing EGFR mutation (civic.EID:2997).

#	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: May 26, 2024

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