Draft of Clinical Genomics extension to the FHIR Observation for reporting of a DNA variant.
Scope of Release 1: Does not include interpretation. Constrained to a DNA variant type which is supported by HGVS nomenclature. Testing platforms supported
include NGS, Sanger Sequencing, and testing kits.
Due date extended to December 4, 2015
Therefore, consider extending to support HLA typing, CNV, and Translocations
Analysis of FHIR extensions stemming from Gil’s work: http://smartgenomics.wikispaces.com/GeneticObservation
Similar to genetic disease or medication assessed
Out of Scope for release 1
Equal to sequence variation
In Scope – Needs further definition
Need to extend to support unambiguous definition of a variant (if available) and additional
extension for cross testing platform support
Need further definition

traitAssesed - Target trait being studied

variant - HGVS identifier of an variant being
associated with the phenotype studied
o
genotype - Reference to a Sequence
resource indicating the patient's genotype
on a variant
o
interpretation - Interpretation of a variant's
effect on the patient's phenotype
Out of scope for release 1
o
comment - A comment of the variant's
effect
Unstructured data for variant effect
Out of scope for release 1
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Tuesday, September 09, 2014
Suggested – preliminary draft
Suggested Name
(names in bold come from previous
HL7 CG standards)
Constraints
Definition
GenomeBuild.version

Genomic Reference Sequence Identifier 

Chromosome



GenomicReferenceSequence.version
o
o
o
Genomic start
o
o
o
Genomic stop
o
o
o
Reference allele
Observed allele
Gene
cDNAReferenceSequence.version
cDNASequenceVariation using HGVS
Nomenclature
Exon
Gene Identifier
Transcript Reference Sequence Identifier
DNA Sequence Variation Identifier
HGNC
NCBI or EBI
HGVS
DNA Region Name
cDNAChangeType
DNA Sequence Variation Type
Consider linking to SO
Ontology terms
Consider linking to SO
Ontology terms
NCBI or EBI
HGVS
RNAReferenceSequence.version
AASequenceVariation using HGVS
Nomenclature
AAChangeType
Amino Acid Change
Amino Acid Change Type
CommonVariantSynonym
Genomic source class
Allele Name
Genomic source class
Allelic State
Allelic State
Consider linking to SO
Ontology terms
(germline, somatic,
prenatal, unknown
genomic origin, likely
germline, likely somatic,
likely fetal)
Heteroplasmic,
Homoplasmic,
Homozygous,
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Tuesday, September 09, 2014
Heterozygous,
Hemizygous
Notes from Sept 2, 2014
Continued discussion of tagging some data as derived.
Attendees: Grant Wood, Bob Milius, Scott Bolte, Mollie Ullman-Cullere, Larry Babb, and Siew Lam
Primary data vs. interpretation
--> what the physician gets it the primary data (within the EHR), downstream is the interpretive data
--> However, the lab will have different primary data, more upstream . Primary data is the level at which the
stakeholder would revert to for a recalculation. If genomic, cDNA, Amino Acid and Allele/Common name are reported from
the laboratory, uses should not use one of these elements to recalculate another, because the laboratory likely detected
the mutation at one level (genomic) and made decisions at another level (amino acid change). Therefore, the mutation
definition should be used in its entirety. If something is inaccurate, the test should be rerun or re-reported.
Derived
– should not be used to tag the translation to cDNA/AA change or calculation of genomic coordinates (from cDNA).
Derived should be used when the presence of a variant is assumed due to presence of another which was measured e.g. *
alleles
 If desire is to denote the initial context of testing, should we use ‘testing platform’ and add ‘providence’
(of the test). providence = source of the information (who e.g. ) (when) what and how
 LMM’s NGS pipeline 1.0 see how it works here with link to website (e.g. BI pipeline details etc...) In the
future this might be held in NCBI’s genetic test registry
 Look for definition of providence and derived in FHIR
Larry – send best representation of variant for additional downstream usage
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Tuesday, September 09, 2014
IOM – establishing data elements and EHR should have to store genetic/genomic information
Grant to be attending the meeting
Germline list and Somatic elements --> Grant to send out list of somatic elements.
Notes from Sept 9 2014 con call
Attendees: Amnon Shabo, Grant Wood, Bob Milius, Mollie Ullman-Cullere, Scot Bolte, Siew Lam, Gil Alterovitz, Perry Mar, Vanderbilt: Jonathan Holt, Ari Taylor,
Jeremy Warner,Marc Beller
How do you support the use cases where the patient is mosaic or there is chimerism (e.g. from a stem cell transplant)? Should germline/somatic designation be
at the specimen level?
Outcome
Germline needs to be well defined. Germline = background genome
–
–
germline/somatic designation should be used at the mutation level - drawing from previous work and maintaining alignment with ClinVar, COSMIC, and
other mutation knowledgebases.
a qualifier needs to be created and can be used to denote that the mutation is resulting from a ‘chimera’
Qualifier would be mosaic or chimera (preferred)
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Tuesday, September 09, 2014