proteinSequenceConsequence-ex1.yaml

id: civic.mpid:33
type: CategoricalVariant
description: >-
  EGFR L858R has long been recognized as a functionally significant mutation in cancer,
  and is one of the most prevalent single mutations in lung cancer. Best described in
  non-small cell lung cancer (NSCLC), the mutation seems to confer sensitivity to first
  and second generation TKI's like gefitinib and neratinib. NSCLC patients with this
  mutation treated with TKI's show increased overall and progression-free survival, as
  compared to chemotherapy alone. Third generation TKI's are currently in clinical trials
  that specifically focus on mutant forms of EGFR, a few of which have shown efficacy in
  treating patients that failed to respond to earlier generation TKI therapies.
name: EGFR L858R
constraints:
  - type: DefiningAlleleConstraint
    allele: vrs.json#/ga4gh:VA.kgjrhgf84CEndyLjKdAO0RxN-e3pJjxA
    relations:
      - primaryCode: translates_from
  - type: FeatureContextConstraint
    featureContext:
      id: normalize.gene.hgnc:3236
      extensions:
        - name: symbol_status
          value: approved
        - name: approved_name
          value: epidermal growth factor receptor
      conceptType: Gene
      name: EGFR
      primaryCode: hgnc:3236
      mappings:
        - coding:
            system: https://www.genenames.org
            code: hgnc:3236
          relation: exactMatch
        - coding:
            system: https://www.ensembl.org
            code: ensembl:ENSG00000146648
          relation: relatedMatch
        - coding:
            system: https://www.ncbi.nlm.nih.gov/gene/
            code: ncbigene:1956
          relation: relatedMatch
members:
  - vrs.json#/ga4gh:VA.7jX7fHgVEqx4C4jMRyZOH0ZBHnLn7_gJ
  - vrs.json#/ga4gh:VA.3_FsKSUHEdurPIw5gqpw6g0_Ga0TEXQh
  - vrs.json#/ga4gh:VA.zpv3dW34z8jioKL-NtbGc0fa9clsgAZT
  - vrs.json#/ga4gh:VA.BJOtfUhZMooMJUO4FjxHXTEimrKXtF0i
aliases:
  - LEU858ARG
  - rs121434568
mappings:
  - coding:
      code: CA126713
      system: https://reg.clinicalgenome.org/
    relation: relatedMatch
  - coding:
      code: '16609'
      system: https://www.ncbi.nlm.nih.gov/clinvar/variation/
    relation: relatedMatch
  - coding:
      code: '376282'
      system: https://www.ncbi.nlm.nih.gov/clinvar/variation/
    relation: relatedMatch
  - coding:
      code: '376280'
      system: https://www.ncbi.nlm.nih.gov/clinvar/variation/
    relation: relatedMatch
  - coding:
      code: rs121434568
      system: https://www.ncbi.nlm.nih.gov/snp/
    relation: relatedMatch
extensions:
  - name: CIViC representative coordinate
    value:
      chromosome: '7'
      start: 55259515
      stop: 55259515
      reference_bases: T
      variant_bases: G
      representative_transcript: ENST00000275493.2
      ensembl_version: 75
      reference_build: GRCh37
  - name: CIViC Molecular Profile Score
    value: 379
  - name: Variant type
    value:
      code: SO:0001583
      system: http://www.sequenceontology.org/browser/current_release/term/
      name: missense_variant