ISO/TS 20428:2017

TECHNICAL ISO/TS
SPECIFICATION 20428
First edition
2017-05
Health informatics — Data elements
and their metadata for describing
structured clinical genomic sequence
information in electronic health
records
Informatique de santé — Éléments de données et leurs métadonnées
pour décrire l’information structurée de la séquence génomique
clinique dans les dossiers de santé électroniques
Reference number
©
ISO 2017
© ISO 2017, Published in Switzerland
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ii © ISO 2017 – All rights reserved

Contents Page
Foreword .v
Introduction .vi
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 1
4 Abbreviated terms . 5
5 Use case scenario . 6
6 Composition of a clinical sequencing report . 7
6.1 General . 7
6.2 Overall interpretation in summary . 8
6.3 Detailed contents . 8
7 Fields and their nomenclature of required data . 9
7.1 General . 9
7.2 Clinical sequencing orders .10
7.2.1 General.10
7.2.2 Clinical sequencing order code .10
7.2.3 Date and time .10
7.2.4 Specimen information .11
7.3 Information on subject of care .11
7.3.1 General.11
7.3.2 Subject of care identifiers . .11
7.3.3 Subject of care name .11
7.3.4 Subject of care birth date .11
7.3.5 Subject of care sex.11
7.3.6 Subject of care ethnicity .11
7.4 Information on legally authorized person ordering clinical sequencing .11
7.4.1 General.11
7.5 Performing laboratory .12
7.5.1 General.12
7.5.2 Basic information on performing laboratory .12
7.5.3 Information on report generator .12
7.5.4 Information of legally confirmed person on sequencing report .12
7.6 Associated diseases and phenotypes .12
7.7 Biomaterial information .12
7.7.1 General.12
7.7.2 Types of sample .12
7.7.3 Genomic source class in biomaterial .12
7.7.4 Conditions of specimen that may limit adequacy of testing .12
7.8 Genetic variations .13
7.8.1 General.13
7.8.2 Gene symbols and names .13
7.8.3 Sequence variation information .13
7.9 Classification of variants .14
7.9.1 General.14
7.9.2 Classification of variants based on the pathogeny .14
7.9.3 Classification of variants based on clinical relevance .15
7.10 Recommended treatment .15
7.10.1 General.15
7.10.2 Classification of variants based on clinical relevance .15
7.10.3 Clinical trial information .15
7.10.4 Known protocols related to a variant .16
7.10.5 Other recommendation .16
7.11 Addendum .16
8 Fields and their nomenclature of optional data .16
8.1 General .16
8.2 Medical history .17
8.3 Family history/Pedigree information .17
8.4 Reference genome version .17
8.5 Racial genomic information .18
8.6 Genetic variation .18
8.7 Detailed sequencing information .18
8.7.1 Clinical sequencing date .18
8.7.2 Quality control metrics .18
8.7.3 Base calling information .18
8.7.4 Sequencing platform information .19
8.7.5 Analysis platform information .20
8.8 References .20
Annex A (informative) Example structure of clinical sequencing report .21
Annex B (informative) Example layout of clinical sequencing report .28
Bibliography .32
iv © ISO 2017 – All rights reserved

Foreword
ISO (the International Organization for Standardization) is a worldwide federation of national standards
bodies (ISO member bodies). The work of preparing International Standards is normally carried out
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electrotechnical standardization.
The procedures used to develop this document and those intended for its further maintenance are
described in the ISO/IEC Directives, Part 1. In particular the different approval criteria needed for the
different types of ISO documents should be noted. This document was drafted in accordance with the
editorial rules of the ISO/IEC Directives, Part 2 (see www .iso .org/ directives).
Attention is drawn to the possibility that some of the elements of this document may be the subject of
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on the ISO list of patent declarations received (see www .iso .org/ patents).
Any trade name used in this document is information given for the convenience of users and does not
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For an explanation on the voluntary nature of standards, the meaning of ISO specific terms and
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World Trade Organization (WTO) principles in the Technical Barriers to Trade (TBT) see the following
URL: w w w . i s o .org/ iso/ foreword .html.
The committee responsible for this document is ISO/TC 215, Health informatics.
Introduction
Based on the rapid advancement of sequencing technologies, clinical sequencing has been highlighted
as one of methods to realize personalized medicine and precision medicine. There are lots of sequencing
[1]
data in the public domain with clinical information . In addition, genome-scale clinical sequencing
[2]
is being adopted broadly in medical practice . Many hospitals have started to sequence patients’
whole genome, whole exome, or targeted genes using the next generation sequencing technologies.
These genomic data obtained by next generation sequencing technologies can be used for both clinical
purposes to diagnose patients and choose the right medications and research purposes. Therefore, the
management of genomic and clinical data is increasingly highlighted to precision medicine, clinical trial
[3]
and translational research .
However, until now, there is no international standard for representing clinical sequencing results with
a structured format for electronic health records, in consequence, the necessary genomic test results
are not efficiently delivered to the clinicians. There are a few related standards for modelling genetic
testing results (i.e. ISO 25720 and several HL7 documents from HL7 clinical genomics working group).
However, these standards or drafts are mainly focused on the traditional genetic testing results for a
single gene test. Based on the rapid development and adoption of next generation sequencing techniques
which can detect diverse genetic variants in genome level, there is, therefore, still a need to develop a
[4]
standard to present clinical sequencing data in such a way they become useful for clinicians .
To implement a structured clinical sequencing report in electronic health records, all necessary data
fields should be defined and the metadata for each chosen field should be defined. For example, it
needs to be determined which vocabulary, in particular gene descriptions and/or disease codes, can be
applied in particular fields. In ISO TC 215, GSVML (Genomic Sequence Variation Markup Language) was
proposed for interoperability of genomic variants, especially for single nucleotide polymorphism (SNP)
[5] [6]
data . HL7 is also developing a domain analysis model for genomics using HL7 version 3 and fast
[7]
healthcare interoperability resources (FHIR) . Recently, to facilitate genomic information, SMART on
[8],[9]
FHIR Genomics has been developed . The Clinical Data Interchange Standard Consortium (CDISC)
[10]
published a study data tabulation model implementation guide: pharmacogenomics/genetics .
Several other international organizations such as Global Alliance for Genomics and Health (GA4GH),
Actionable Genome Consortium, and Displaying and Integrating Genetic Information Through the EHR
(DIGITizE) of Institute of Medicine in US, tried to develop the similar standards. The working group
of the American College of Medical Genetics and Genomics Laboratory Quality Assurance Committee
[11]
published the ACMG clinical laboratory standards for next-generation sequencing . In addition,
web-based tools become available that link genotypic information to phenotypic information, and
[12]
exchanging information and using it in personalized medicine can be very helpful .
In this document, to enable the standard use of patient genomic data from clinical sequencing for
healthcare purposes as well as for clinical trials and research, the metadata for a clinical sequencing
report for electronic health records will be developed. It further explains how and where particular
appropriate terminological systems that describe the genomes and/or diseases can be applied in
these fields. By defining the necessary fields with structured format based on coded data that adhere
themselves to terminological principles such as concept representation and governance, this document
can help implement clinical decision support service.
vi © ISO 2017 – All rights reserved

TECHNICAL SPECIFICATION ISO/TS 20428:2017(E)
Health informatics — Data elements and their metadata
for describing structured clinical genomic sequence
information in electronic health records
1 Scope
The document defines the data elements and their necessary metadata to implement a structured
clinical genomic sequencing report and their metadata in electronic health records particularly
focusing on the genomic data generated by next generation sequencing technology.
This document
— defines the composition of a structured clinical sequencing report (see Clause 5),
— defines the required data fields and their metadata for a structured clinical sequencing report (see
Clause 6),
— defines the optional data (see Clause 7),
— covers the DNA-level variation from human samples using whole genome sequencing, whole exome
sequencing, and targeted sequencing (disease-targeted gene panels) by next generation sequencing
technologies. Though whole transcriptome sequencing and other technologies are important to
provide better patient care and enable precision medicine, this document only deals with DNA-level
changes,
— covers mainly clinical applications and clinical research such as clinical trials and translational
research which uses clinical data. However, the necessary steps such as de-identification or consent
from patient should be applied. The basic research and other scientific areas are outside the scope
of this document,
— does not cover the other biological species, i.e. genomes of viruses and microbes, and
— does not cover the Sanger sequencing methods.
2 Normative references
There are no normative references in this document.
3 Terms and definitions
For the purposes of this document, the following terms and definitions apply.
ISO and IEC maintain terminological databases for use in standardization at the following addresses:
— ISO Online browsing platform: available at http:// www .iso .org/ obp
— IEC Electropedia: available at http:// www .electropedia .org/
3.1
allele
one of several alternate forms of a gene which occur at the same locus on homologous chromosomes
and which become separated during meiosis and can be recombined following fusion of gametes
[SOURCE: ISO 16577:2016, 3.6]
3.2
benign
alterations with very strong evidence against pathogenicity
3.3
biomaterial
materials taken from the human body such as tissue, blood, plasma or urine
3.4
chromosome
structure that comprises discrete packages of DNA and proteins that carries genetic information which
condense to form characteristically shaped bodies during nuclear division
[SOURCE: ISO 19238:2014, 2.7]
3.5
clinical sequencing
next generation sequencing or later sequencing technologies with human samples for clinical practice
and clinical trials
3.6
ClinVar
freely accessible, public archive of reports of the relationships among human variations and phenotypes,
with supporting evidence
Note 1 to entry: http:// www .ncbi .nlm .nih .gov/ clinvar/ .
3.7
copy number variation
CNV
variation in the number of copies of one or more sections of the DNA
3.8
Catalogue of Somatic Mutations in Cancer
COSMIC
online database of somatically acquired mutations found in human cancer
Note 1 to entry: http:// cancer .sanger .ac .uk/ cosmic.
3.9
dbSNP
database of SNPs provided by the US National Center for Biotechnology Information (NCBI)
Note 1 to entry: https:// www .ncbi .nlm .nih .gov/ SNP/ .
3.10
deletion
mutation in which a part of a chromosome or a sequence of DNA is lost during DNA replication
3.11
deoxyribonucleic acid
DNA
molecule that encodes genetic information in the nucleus of cells
[SOURCE: ISO 25720:2009, 4.7]
3.12
DNA sequencing
determining the order of nucleotide bases (adenine, guanine, cytosine and thymine) in a molecule of DNA
Note 1 to entry: Sequence is generally described from the 5’ end.
2 © ISO 2017 – All rights reserved

[SOURCE: ISO/TS 17822-1:2014, 3.20]
3.13
exome
part of the genome formed by exons
3.14
gene
basic unit of hereditary material that encodes and controls the expression of a protein or protein subunit
[SOURCE: ISO 11238:2012, 2.1.16]
3.15
gene panel
technique for sequencing the targeted genes in a genome
3.16
genomic medicine
medical discipline that involves using genomic information about an individual as part of their
clinical care (e.g. for diagnostic or therapeutic decision-making) and the health outcomes and policy
implications of that clinical use
3.17
germline
series of germ cells each descended or developed from earlier cells in the series, regarded as continuing
through successive generations of an organism
3.18
indel
insertion (3.19) or/and deletion (3.10)
3.19
insertion
addition of one or more nucleotide base pairs into a DNA sequence
3.20
inversion
chromosome rearrangement in which a segment of a chromosome is reversed end to end
3.21
large indel
insertion or deletion up to ~1 kb
3.22
likely benign
alterations with strong evidence against pathogenicity
Note 1 to entry: Targeted testing of at-risk family members not recommended.
3.23
likely pathogenic
alterations with strong evidence in favor of pathogenicity
3.24
pathogenic
characteristic that is objectively measured and evaluated as an indicator of normal biological processes,
pathogenic processes, or pharmacologic responses to a therapeutic intervention
3.25
prenatal/fetal
biomaterial sample of fetuses before birth
Note 1 to entry: Prenatal/fetal DNA sequencing: Reading the DNA of foetuses to diagnose Mendelian disease of
unborn child.
3.26
sequence read
read
fragmented nucleotide sequences which are used to reconstruct the original sequence for next
generation sequencing technologies
3.27
read type
type of run in the sequencing instrument
Note 1 to entry: It can be either single-end or paired-end.
Note 2 to entry: Single-end: Single read runs the sequencing instrument reads from one end of a fragment to the
other end.
Note 3 to entry: Paired-end: Paired end runs read from one end to the other end, and then start another round of
reading from the opposite end.
3.28
reference sequence
digital nucleic acid sequence database, assembled by scientists as a representative example of
human genome
3.29
ribonucleic acid
RNA
polymer of ribonucleotides occurring in a double-stranded or single-stranded form
[SOURCE: ISO 22174:2005, 3.1.3]
3.30
sequence variation
DNA sequence variation
variation
differences of DNA sequence among individuals in a population
Note 1 to entry: Variation implies CNV (3.7), deletion (3.10), insertion (3.19), indel (3.18), small indel (3.32), large
indel (3.20), and SNP (3.31).
[SOURCE: ISO 25720:2009, 4.8]
3.31
single nucleotide polymorphism
SNP
single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population
Note 1 to entry: Pronounced “snip”.
[SOURCE: ISO 25720:2009, 4.23]
3.32
small indel
insertion or deletion of 2 ~100 nucleotides
4 © ISO 2017 – All rights reserved

3.33
somatic cell
cells of the body in contrast to the germ line cells
3.34
biological specimen
biospecimen
specimen
sample of tissue, body fluid, food, or other substance that is collected or acquired to support the
assessment, diagnosis, treatment, mitigation or prevention of a disease, disorder or abnormal physical
state, or its symptoms
3.35
subject of care
any person who uses, or is a potential user of, a health care service
[SOURCE: ISO/TS 22220:2011, 3.2]
3.36
target capture
method to capture genomic regions of interest from a DNA sample prior to sequencing
3.37
uncertain significance
alterations with limited and/or conflicting evidence regarding pathogenicity
3.38
whole exome sequencing
WES
technique for sequencing all the protein-coding genes in a genome
3.39
whole genome sequencing
WGS
technique that determines the complete DNA sequence of an organism’s genome at a single time
4 Abbreviated terms
This list of abbreviated terms includes all abbreviations used in this document.
ACMG the American College of Medical Genetics and Genomics
COSMIC the Catalogue of Somatic Mutations in Cancer
CPIC the Clinical Pharmacogenetics Implementation Consortium
EBI the European Bioinformatics Institute
FHIR Fast Healthcare Interoperability Resources
HGNC the HUGO Gene Nomenclature Committee
HGVS the Human Genome Variation Society
HUGO the Human Genome Organization
IARC International Agency for Research on Cancer
LOINC Logical Observation Identifiers Names and Codes
NCBI National Center for Biotechnology Information
NCCN National Comprehensive Cancer Network
NGS Next Generation Sequencing
SNP Single Nucleotide Polymorphism
SPREC Standard Preanalytical Code
WES Whole Exome Sequencing
WGS Whole Genome Sequencing
5 Use case scenario
The abstracted use case for generating a clinical genomic sequencing report is demonstrated in
Figure 1. At first, the clinician will place a clinical sequencing order using the electronic health records
system (step 1 in Figure 1). After the order, a responsible department will request DNA sequencing
to the sequencing facility (step 2). This sequencing facility can be located inside of the hospital or
be an independent sequencing facility outside the hospital (step 3). When confirming the order, the
sequencing facility will request a sample from the patient (step 4). The hospital will collect a sample
from the patient (steps 5 and 6). The pre-collected samples, i.e. biobank sample, the samples acquired
by a previous laboratory or pathology orders, can be used as well. The biomaterial from the patients
will be delivered to the sequencing facility (step 7). After receipt, the sequencing facility will perform a
sequencing analysis (step 8) and generate the report (step 9). This report will be sent to the requested
hospital (step 10), and the report will be updated in the electronic health record system (step 11).
The ordering clinician will be notified of the completion of the sequencing order (step 12). Finally, the
ordering clinician will make a diagnosis or give a proper treatment (step 13). A patient can have a copy
of final report.
6 © ISO 2017 – All rights reserved

Figure 1 — Abstracted flow of generating clinical genomic sequencing report
The possible use cases for the clinical sequencing orders are well described in “HL7 VERSION 3 Domain
[6]
Analysis Model: Clinical Sequencing” .
6 Composition of a clinical sequencing report
6.1 General
The structured clinical sequencing report may mainly consist of two parts: the summary part and the
detailed contents part as in Figure 2. The summary part can include the subset of required fields to help
[13],[14]
clinicians quickly overview the most important findings concisely . The detailed content part
should contain all required fields and the selected optional fields.
This document only defines the data elements and their metadata for the structured clinical sequencing
report in electronic health records. Therefore, its layout can be designed based on the institutional
decision if all elements are included as in this document.
Summary
Detailed contents
Detailed DeDeDeDeDeDeDeDeDettttttttttaaaaaaaaailililililililiillededededededededede pageppppppppppaaaaaaaaagggggggggeeeeeeeeeesssssssssss
Detailed pages
Detailed pages
̶Subset of required fields
Ex)
̶Required fields
̶Patient information
̶Type of samples
-R-Requiequirreed ieldsd ields
-Required ields
̶Variants information
-Required ields
̶Recommended treatments
̶̶Optional ields
̶Overall interpretation
--Optional Optional ieldsields
-Optional ields
̶Identiied, Not identiied,
-Optional ields
Inconclusive, Carrier
Figure 2 — Composition of a clinical sequencing report
6.2 Overall interpretation in summary
The summary part should report the overall interpretation of a genomic test with a succinct description:
identified, not identified inconclusive, or carrier. Table 1 summarizes each interpretation. “Identified”
represents a detection of a variant that explains a patient’s condition. “Not identified” means no variants
identified of likely relevance to the diagnostic indication. “Inconclusive” is a clear explanation of the
patient’s condition was not found either due to only variants of unknown significance being identified
or due to only a single heterozygous variant identified for a recessive condition. “Carrier” represents
[11]
the identification of variants of recessive carrier screening tests .
Table 1 — Overall interpretation in the summary part
Interpretation Remarks
Identified detection of a variant that explains a patient’s condition
Not identified no variant identified of likely relevance to the diagnostic indication
Inconclusive a clear explanation of the patient’s condition was not found
Carrier identification of variants of recessive carrier screening tests
6.3 Detailed contents
The detailed contents consist of two parts such as the required and optional fields. The detailed content
part should contain all required fields and the selected optional fields. HL7 Implementation Guide for
CDA Release 2 Genetic Testing Report can be a good example. However, HL7 Genetic Testing Report only
focuses on the single gene test and does not cover next generation sequencing technology.
The required fields mainly focus on helping clinicians by providing the necessary genomic information,
interpretation results, and the related treatments. They include all necessary fields for clinical
practice. The optional fields give more detailed information to clinicians. They also can facilitate
translational research with the necessary steps such as de-identification or consent from the patient. In
Reference [13], the data fields for molecular genetic report template were categorized into “required,”
“optional,” “possible,” and “not necessary” based on the survey. The data fields in this document were
re-categorized to implement a structured clinical sequencing report by reviewing the existing free-text
format sequencing report.
8 © ISO 2017 – All rights reserved

7 Fields and their nomenclature of required data
7.1 General
The required fields are chosen for clinical practice. The information which can be only described in the
clinical sequencing report is included in the required fields to minimize the length of clinical sequencing
report. The other relevant information can be included in the optional fields or other clinical reports in
the electronic health records. The summary of data elements and their metadata are shown in Table 2.
Table 2 — Data elements and their metadata for required fields
Data elements Metadata (Primary)
Order code LOINC
Clinical sequencing
Information on se-
order code
TEXT
quencing order
Order date
Specimen collection
date
Clinical sequencing orders
Date and time Order received date ISO 8601
Report date
Addendum creation
date
Specimen information ISO/TS 22220:2011
Identifiers
ISO/TS 22220:2011
Name
Information on subject
Birth date ISO 8601
of care
Sex ISO/TS 22220:2011
Ethnicity HL7 v3 Code System Race
Information of legally authorized person ordering clinical se-
ISO/TS 27527:2010
quencing
Basic information TEXT
Information of report generator TEXT
Performing laboratory
Information of legally confirmed person on
ISO/TS 27527:2010
sequencing report
Associated diseases and phenotypes ICD
Type of sample SPREC
Biomaterial information Genomic source class in biomaterial LOINC
Conditions of specimen TEXT
Gene symbols and names HGNC
Notation HGVS
Genetic variations
Sequence variation
Effects of variants TEXT
information
Sequence variant ID Database unique ID
ENUM (“Pathogenic”, “Likely pathogenic”,
Pathogeny “Unknown significance”, “Likely benign”,
Classification of vari-
a
“Benign”)
ants
ENUM (“Identified,” “Likely identified”, “Un-
Clinical relevance
certain”, “Not identified”)
a
ENUM represents the contents should be chosen among the given category.
Table 2 (continued)
Data elements Metadata (Primary)
Medication ISO 11615
Clinical trial information Clinical trial ID
Recommended treatment
Known protocols related to a variant TEXT
Other recommendation TEXT
a
ENUM represents the contents should be chosen among the given category.
7.2 Clinical sequencing orders
7.2.1 General
When a clinician orders a clinical genomic sequencing, the order code and the required date information
should be given.
7.2.2 Clinical sequencing order code
7.2.2.1 Order code
The relevant clinical sequencing orders should be represented by LOINC (Logical Observation
Identifiers Names and Codes) with used LOINC coding system version. Unfortunately, there are not
LOINC codes for those sequencing orders, but only molecular genetic code until now. In the meantime,
other international, national, or institutional coding system can be alternatively used, for example, CPT
(Current Procedure Terminology) in US has the codes for sequencing.
7.2.2.2 Information on sequencing order
If order code cannot fully describe the purpose of the clinical sequencing, the detailed description of the
sequencing can be added as free text, for example, the sequencing panel name with gene information.
7.2.3 Date and time
For a clinical sequencing report, diverse date and time should be reported due to time delay. All date
and time in the report should be represented by ISO 8601.
7.2.3.1 Order date
Order date is the date which clinician ordered the necessary clinical genomic sequencing.
7.2.3.2 Order received date
Order received date is the date that the performing laboratory received and confirmed the clinical
genomic sequencing order.
7.2.3.3 Specimen collection date
Specimen collection date indicates the date when specimen taken from patient or tissue.
7.2.3.4 Report date
Report date is the date which the performing laboratory generates the sequencing report.
10 © ISO 2017 – All rights reserved

7.2.3.5 Addendum creation date
Addendum creation date is the date that the performing laboratory creates the addendum of the
previous report using up-to-date information. The analysis pipelines or referred database is updated
due to technology advancement. The reference sequence is regularly updated. In addition, it should be
updated due to legal aspects. Therefore, the performing laboratory should create the addendum of the
existing sequencing report based on the clinician’s request or law enforcement.
7.2.4 Specimen information
The specimen information can be represented by subject of care identifier type code of ISO 22220:2011.
EXAMPLE 13-S-048435_A1 - Pathology Number: ISO 22220:2011 (SOC identifier designation: 13-S-048435_
A1, SOC identifier geographic area: 1 (local), SOC identifier issuer: AMC (ABC Medical Center), 02 (speciality
number - pathology).
7.3 Information on subject of care
7.3.1 General
Information on subject of care whose specimen was sequenced should be represented by ISO 22220:2011.
EXAMPLE 12345678 - ISO 22220:2011 (SOC identifier designation: 12345678, SOC identifier geographic
area: 1 (local), SOC identifier issuer: AMC (ABC Medical Center), 01 (unique identifier for issuer).
7.3.2 Subject of care identifiers
The unique identifiers for subjects of care should be included.
7.3.3 Subject of care name
The subject of care name should be given.
7.3.4 Subject of care birth date
The subject of care’s birth date should be given to calculate the patient’s age. Birth date should be
represented by ISO 8601.
7.3.5 Subject of care sex
The subject of care’s sex should be represented by ISO 22220:2011.
7.3.6 Subject of care ethnicity
The ethnicity of the subject of care should be notified to represent his or her genetic origin. The
ethnicity information should be represented by HL7 v3 Code System Race (https:// www .hl7 .org/ fhir/
v3/ Race/ index .html). Alternatively, if there are national standards, those coding systems can be used,
[15]
for example, US FDA guidance for Industry – Collection of Race and Ethnicity Data in Clinical Trials .
7.4 Information on legally authorized person ordering clinical sequencing
7.4.1 General
Information on legally authorized person who ordered clinical sequencing might be represented by
ISO/TS 26527:2010.
The detailed items of this field such as the name of ordering physician, his/her medical speciality, or
contact numbers, can be chosen by the implementing hospitals or laboratories.
7.5 Performing laboratory
7.5.1 General
The laboratory that performs the sequencing should be given.
7.5.2 Basic information on performing laboratory
The name of performing laboratory and contact points such as phone numbers or emails should be
notified. This information can be given in free text until the relevant standard will be published.
7.5.3 Information on report generator
Information on subject of provider who generated a report of sequencing results should be reported. It
can be represented by ISO/TS 26527:2010 or by free text.
7.5.4 Information of legally confirmed person on sequencing report
Information of legally confirmed physician might be given by ISO/TS 26527:2010.
7.6 Associated diseases and phenotypes
If possible, associated diseases and phenotypes should be included using ICD codes or SNOMED-CT
code. Other phenotypes that are not classified by ICD or SNOMED-CT can be represented by Human
Phenotype Ontology (http:// human -phenotype -ontology .github .io/ ).
Since even single variant can have multiple associated phenotypes including diseases, all possible
associated diseases should be listed based on the confidence level.
In this field, only diseases or phenotypes those are associated with the found variants should be
indicated. The previously known diseases of subject of care, which are not associated with the variants,
should be excluded in this field.
7.7 Biomaterial information
7.7.1 General
The information on the specimen from patient should be described.
7.7.2 Types of sample
Types of samples can be represented by Standard Preanalytical Code (SPREC) V2.0 of International
[16]
Society for Biological and Environmental Repositories .
EXAMPLE BLD (Blood), BUF (buffy coated), non-blood tissue (CEN), semen (SEM).
7.7.3 Genomic source class in biomaterial
The genomic source of patient’s sample should be categorized as follows: 1) germline, 2) somatic, 3)
prenatal/fetal, 4) likely germline, 5) likely somatic, 6) likely prenatal/fetal, or 7) unknown genomic
origin. This category is based on LOINCS answer list LL378-1.
7.7.4 Conditions of specimen that may limit adequacy of testing
The specific conditions that can affect or limit the adequacy of genomic sequencing should be described
in text format.
EXAMPLE Tumor purity information should be given in percentage.
12 © ISO 2017 – All rights reserved

7.8 Genetic variations
7.8.1 General
All found variants should be listed in the report according to their relevance to the patient’s indication
for testing. However, in the required field, the variants that have the associated treatments should be
listed. The other variants can be listed in the optional fields.
As in 7.9, classification of variants can be categorized based on the founding variant has a proper
treatment. In the clinical setting, the variants without proper treatment have no meaning to the
clinicians. Therefore, only variants with treatments should be included in the required field.
The variants information should include the following information.
7.8.2 Gene symbols and names
The gene symbol and name which contains the founding variants should be represented by HGNC
(HUGO (Human Genome Organization) Gene Nomenclature Committee). The HGNC approved gene
symbol and
...