Design Comments: The id attribute is a globally unique instance identifier for the Genetic Loci act. The Genetic Loci id should remain constant across all genetic variation analysis interpretation revisions that derive from a common original genetic test observation or set of observations.

Design Comments: The Genetic Loci title is an optional attribute used to provide a short print label when the genetic test group/panel can not be defined by a coded reference (see the value field) to a gene testing database.

Design Comments: The Genetic Loci text field is used when the suite of genes or genetic locus that are part of the loci group need human readability. A free text description of the Loci for visual display or reporting can be included in this text field. Note that comments should be added through the A_Annotation CMET and not through the text attribute which is supposed to contain a complete rendering of the observation.

Design Comments: This required attribute allows the sender to define the confidentiality status for all information about the Genetic Loci analysis. This confidentiality code will be conducted to all acts under the Genetic Loci, unless it is overridden by a different value at a lower level.

Design Comments: This optional attribute defines one or more reasons (administrative in nature) that a Genetic Loci instance is being created. If the interpretation code attribute (see below) is populated, then the clinical practice or research reason shall be provided by traversing the RSON act relationship, in order to provide the semantic context for the interpretation.

Design Comments: The value attributes identifies the set of loci through a name drawn from a recognized terminology (e.g., HLA haplotypes) or through compositional notations or through the encapsulation of raw data (e.g., SNP genotyping results).

Design Comments: This negation indicator is an optional attribute that allows the sender to indicate that a Genetic Loci was not found. The Negation Indicator is a Boolean that is set to “True” when, for example, a specific set of loci (e.g., SNP haplotype) was looked for and wasn’t found in the subject specimen.

Design Comments: This optional attribute defines one or more interpretations derived from a genetic variation test whose “raw” data may or may not be included in the instance. The interpretation code should carry a phenotypic interpretation when the interpretation can be expressed as a single (or small number of) short, concise statements that are easily coded. If a more elaborate discussion of the phenotype is required, the Phenotype CMET model should be used.

Design Comments: This optional attribute defines one or more methods used to perform the genetic variation analysis. The values for the genetic Loci methodCode are intended to be very high level, and are used to indicate the type(s) for test methods used in the analysis. (e.g. a genotype chip for 8 genes may be combined with sequence results for two additional genes to produce the overall suite of genes combined in the Genetic Loci analysis).

Design Comments: The Genetic Document class is used to connect a human readable supporting or summary document to the genetic analysis as a whole. Note that the Clinical Genomics and Structured Documents Work Groups develop a CDA Implementation guide for Genetic Testing Reports which could then be used as a default in this association. Note that class is essentially a stub and its attributes are taken from the document attributes and represent essential metadata about the document to allow parsing application locating the document

UsageNotes: There are two ways to refer to a clinical document:

1. Populate the id attribute with the document id

2. Place the entire CDA instance within the text attribute

The other attributes in this class are essential data about the document and they are repeated in the document instance itself. It’s meant to ease the parsing process.

Design Comments: The id attribute is a globally unique instance identifier for the Genetic Document. The ID should identify a distinct report instance, with its own effective time. If a second analysis is performed against an update gene database, and a second report generated, then a new Genetic report id should be used as this is a new instance with its own author and effective time. Every Genetic Document should also have another id attribute ‘setId’ which remains constant across all revisions of the document that pertains to the genetic variation instance.

Design Comments: The Genetic Document code is required, and further identifies the type of genetic document (e.g., genetic variations report, gene expression testing report, etc.)

Design Comments: Every Genetic Document instance has an optional title, with a data type of ST that allows free text entry of the human readable title of the report.

Design Comments: The text field is used when the report is being referenced from or encapsulated within the text attribute of the Genetic Document act, or a pointer/URL is being provided to locate the report.

Design Comments: This required attribute identifies the point in time that the report was issued. The Genetic Document effective time should thus be equal to or later than the effectiveTime stamp of the Genetic Loci act that is its parent.

Design Comments: This required attribute allows the sender to define the confidentiality status for all information within the genetic document. This confidentiality value may override the confidentiality at the Genetic Loci parent level.

Design Comments: This optional attribute defines human language used to write the report.

Design Comments: A unique id that identifies a group of related documents (see the CDA spec for more details).

Design Comments: When a Genetic Document has been updated/revised and is being re-sent as part of a transmission, the sender may wish to indicate that this is a new version of the document. The Genetic Document act has an optional version number that contains an integer number that indicates the document version.

Design Comments: Use the separation indicator to indicate when a document should not be separated from its associated document (like in the EGFR-KRAS2 use case from HPCGG)

Design Comments: The Genetic Locus class is the critical child act of a Genetic Loci analysis. Each Genetic Locus object defines one gene (or other genetic locus, e.g., unnamed genetic region) to be defined and associated with a suite of observations and statements abut that gene (or locus). A Genetic Locus instance is thus composed of one or more gene (genetic locus) result sets.

UsageNotes: Use code to identify the type of loucs, e.g., gene, biomarker. If code represents a gene, value data type shall be set to CD and contain a code identifying a gene through GenBank GeneID, HUGO name, OMIM ID or any other internationally recognized identification of genes. If the locus doesn’t have a name then the data type should be set to the appropriate type, e.g., ST for locus notation like “10q24.32”.

Design Comments: The id attribute is a globally unique instance identifier for the genetic Locus act. The Genetic Locus id should remain constant across all genetic variation analysis revisions that derive from a common original genetic test observation or set of observations about the locus.

Design Comments: The Genetic Locus code is required, and identifies the genetic locus as a gene, or as a defined locus with semantics such as a genetic bio-marker.

Design Comments: The Genetic Locus title is an optional attribute used to provide a short print label when the gene or genetic region of interest can not be defined by a coded reference (see the value field) to a gene database with human readable display names for its genes.

Design Comments: The Genetic Locus text attribute is used when the gene or genetic locus that is being analyzed needs need human readability. A free text description or multimedia representation of the Genetic Locus for visual display or reporting can be included in this text field. Note that comments should be added through the A_Annotation CMET and not through the text attribute which is supposed to contain a complete rendering of the observation.

Design Comments: This required attribute allows the sender to define the confidentiality level for all information about the Genetic Locus analysis. This confidentiality code will be conducted to all acts under the Genetic Locus, unless it is overridden by a different value at a lower level. If specified, it also supercedes the confidentiality set in the Genetic Loci act.

Design Comments: This optional attribute defines one or more reasons (administrative in nature) that a Genetic Locus instance is being created. If the interpretation code attribute (see below) is populated, then the clinical practice or research reason shall be provided by traversing the RSON act relationship, in order to provide the semantic context for the interpretation. If not used, the Genetic Loci reason applies to the locus.

Design Comments: This negation indicator is an optional attribute that allows the sender to indicate that a Genetic Locus was not found. The Negation Indicator is a Boolean that is set to “True” when, for example, a specific locus (e.g., a genetic bio-marker) was looked for and wasn’t found in the subject specimen.

Design Comments: This optional attribute defines one or more interpretations about the gene or locus derived from a genetic variation test whose “raw” data may or may not be included in the message. The interpretation code should carry a phenotypic interpretation when the interpretation can be expressed as a single (or small number of) short, concise statements that are easily coded. If a more elaborate discussion of the phenotype is required, the Phenotype CMET model should be used.

Design Comments: A related locus that has significant interrelation with the source locus and is not part of this loci set represented in this instance. For example, the target could be a presumed locus that is associated with this locus representing a genetic marker.

Design Comments: The Sequence Variation class is used to describe the subject’s point(s) of genetic variation from a defined reference sequence or normative definition of certain genetic locations (e.g. with a SNP Probe technology).

UsageNotes: Use this associations to the shadow class of Sequence Variation when no allelic data is available or it’s irrelevant to the variation data.

Design Comments: The id attribute is a globally unique instance identifier for the Sequence Variation act. The sequence variation id should identify a distinct variation observation object possibly along with an interpretation. If a second analysis is performed against an update gene database, then a new object should be created assigned with a different id with its own performer and effective time.

Design Comments: The Sequence Variation code is required, and indicates the type of representation used in the value attribute, e.g., dbSNP, HGVS, BSML. Since this class can accommodate a wide range of representations from raw data to compositional notations and codes drawn from a coding system, this code attribute eases the parsing of that class in a way that the parsing application can look in this attribute to know how to parse the content of the value attribute.

Design Comments: The sequence variation title field is used when the sequence variation is relatively complex and needs a short print label for reporting purposes.

Design Comments: The Sequence Variation text field is used when the variation needs human readability. A free text description (or multimedia representation) of the variation for visual display or reporting can be included in this text field. Note that comments should be added through the A_Annotation CMET and not through the text attribute which is supposed to contain a complete rendering of the observation

Design Comments: This required attribute identifies the biologically relevant time of this observation, typically the collection time of the specimen used in the assay or testing. The SequenceVariation.effectiveTime attribute should thus be equal to or earlier than the time of any analysis or interpretation of the data represented by this observation.

Design Comments: The value field is used when the sequence variation can be described in a short concise form, such as the HUGO/HGVS nomenclature and thus carried as a controlled format text value. In other, rare instances where the variation is highly complex, a coded value, or an encapsulated XML blob may also be used as the Sequence Variation value. The value attribute is typed as ANY and should be set accordingly. Note that this class could represent raw data if for example the sequence variation was tested directly and not through full sequencing, but at the same time this class could represent 'bubbled-up' information when it is derived from an observed sequence encapsulated in a Sequence class.

Design Comments: This negation indicator is an optional attribute that allows the sender to indicate that a Sequence Variation represented by the value attribute was not found. In cases when the variation could not be observed due to technical reasons, use the status and reason codes to describe this situation.

Design Comments: This optional field defines one or more interpretations about the sequence variation. The interpretation code should carry a phenotypic interpretation when the interpretation can be expressed as a single (or small number of) short, concise statements that are easily coded. If a more elaborate discussion of the phenotype is required, the Phenotype CMET model should be used.

Design Comments: The Sequence class is used when the full or partial gene sequencing is the primary genetic test method and the sequence variation is being defined by comparing the subject’s observed sequences (usually one for each allele if allelic data was collected) with a reference sequence. A sequence act can be in a definitional mood (moodCode = DEF) when it is being used to define the reference sequence, or in an event mood (EVN) when it is being used to report the observed sequence(s).

UsageNotes: Use this associations to the shadow class of Sequence when no allelic data is available or it’s irrelevant to the sequence data.

Design Comments: The id attribute is a globally unique instance identifier for the Sequence act. The sequence id should remain constant across all genetic variation analysis revisions that derive from a common original sequence observation. The Sequence id may be following the OMG LSID specification if the sequence information has been deposited in a repository and no details are being provide in this particular message instance.

Design Comments: The code attribute indicates the type of representation used in the value attribute, e.g., BSML.

Design Comments: The Sequence title is an optional attribute used to provide a short print label when the sequence of interest needs a human readable print label for reporting. A Sequence title is generally used when interpretation is based on very short, highly targeted sequences.

Design Comments: The text attribute is used when the sequence is being described for human readability purposes. Note that comments should be added through the A_Annotation CMET and not through the text attribute which is supposed to contain a complete rendering of the observation.

Design Comments: This required attribute identifies the biologically relevant time of this observation, typically the collection time of the specimen used in the assay or testing. The Sequence.effectiveTime attribute should thus be equal to or earlier than the time of any analysis or interpretation of the data represented by this observation.

Design Comments: This optional attribute defines one or more reasons (administrative in nature) that a Sequence object is being created. If the interpretation code attribute (see below) is populated, then the clinical practice or research reason shall be provided by traversing the RSON act relationship, in order to provide the semantic context for the interpretation. This attribute is not used if the Genetic Loci or Locus reason code applies to the child sequence observations.

Design Comments: The value field is used when the sequence (reference or observed) is being described within an encapsulated format (e.g. BSML embedded within the HL7 XML).

UsageNotes: ERROR - Business name from Visio is too long and was truncated. Full businessName follows. ((the actual sequence in a recognized bioinformatics content model) (such as BSML

Design Comments: The negation indicator is an optional attribute that allows the sender to indicate that the specific sequence assigned in the value attribute was not found. Note that when, for example, a gene’s maternal or paternal chromosome arm has broken and no sequence read was possible, it should be represented through the status and reason codes and not through the negation indicator.

Design Comments: The interpretation code for a sequence may be used primarily when a well defined gene has only a short sequence needed to identify a single (or small set) of relevant mutations and can thus directly link to a simple, coded interpretation, other wise use the association to the Phenotype CMET.

Design Comments: This attribute is required when in the Sequence observation act is in Event mood, and defines the method used to perform the sequencing of the DNA. Additional supporting method definition may be provided in the Associated Property act.

Design Comments: This recursive association enables the association of an RNA sequence derived from a DNA sequence and a polypeptide sequence derived from the RNA sequence.

Design Comments: The Individual Allele class is used when the sequencing or other genetic method produces observations about the maternal and paternal alleles of the gene or genetic locus, and the observed values and/or variation can be linked to a specific allele. A Genetic Locus instance can thus be composed of one or more allele result sets.

UsageNotes: There could be zero to many IndividualAllele objects in a specific instance. A typical case would be an allele pair, one on the paternal chromosome and one on the maternal chromosome.

Design Comments: The id attribute is a globally unique instance identifier for the Individual Allele act. The Individual Allele ID should remain constant across all genetic variation analysis revisions that derive from a common original genetic test observation or set of observations about the gene or locus.

Design Comments: The Allele title is an optional attribute used to provide a short print label when the allele value of interest needs a human readable print label for reporting.

Design Comments: The text attribute is used when the allele being described does not have a suite of coded allele state defined in a reference database or in the literature, and thus the allele must be described in free text or some multimedia format. Note that comments should be added through the A_Annotation CMET and not through the text attribute which is supposed to contain a complete rendering of the observation.

Design Comments: This optional attribute defines one or more reasons (administrative in nature) that an Individual Allele instance is being created. If the interpretation code attribute (see below) is populated, then the clinical practice or research reason shall be provided by traversing the RSON act relationship, in order to provide the semantic context for the interpretation.

Design Comments: The value attribute is used when the allele being described can be specified by assigning a suite of coded allele states defined in a reference database (e.g., HLA database) or in the literature, otherwise it is possible to use compositional notations or even encapsulate raw data in bioinformatics markups.

Design Comments: This negation indicator is an optional attribute that allows the sender to indicate that the allele was not found. The negation indicator is a Boolean that is set to “True” when, for example, a specific allele (e.g., HLA allele) was looked for and wasn’t found in the subject specimen.

Design Comments: This optional field defines one or more interpretations about the allele The interpretation code should carry a phenotypic interpretation when the interpretation can be expressed as a single (or small number of) short, concise statements that are easily coded. If a more elaborate discussion of the phenotype is required, the Phenotype CMET model should be used.

Design Comments: A related allele that is at a different locus, and has interrelation with the source allele, e.g., translocated duplicates of a gene.