Setting Normative Function: Identification of areas where Standards and Guidelines are required

SETTING NORMATIVE FUNCTION: IDENTIFICATION OF AREAS WHERE STANDARDS AND GUIDELINES ARE REQUIRED

Standards: systems, procedures, technologies that HVP determined shall be used

Guidelines: systems, procedures, technologies that HVP determined to be beneficial to adopt

Arleen AUERBACH

Raymond DALGLEISH

Mauno VIHINEN

Finlay MACRAY

Mireille CLAUSTRES

DATABASE QUALITY AND DATA QUALITY/RELIABILITY

How to ensure data accuracy?

How to avoid data redundancy?

How to ensure nomenclature checking?

How to ensure quality assurance (to organize EQC?)

What is the role of the HVP in database quality?

What is the role of biomedical journals in ensuring variant reporting standards?

SYSTEMATICS of DATABASESLogical database checks (e.g. dates) Ontologies, nomenclatures, vocabularies...

The role of the CURATOR: towards a new concept of a profession with a career structure (ex. a core health service?)

PATHOGENICITY ASSESSMENT (PA) and REPORTING

Familial segregation of variants and associated phenotype?

Annotation (functional significance: in vitro, in vivo and in silico analyses?)

How much phenotype must be attached to data? define a clinical form?

How to accommodate incomplete or variable penetrance in PA?

How to assess polyvariant mutants (modifiers of mutations)?

How to establish the frequency of variants in patients and controls?(ex. 2 patients in a family: how many times the allele is

reported?)

Integration of sometimes discrepant information?

Updating pathogenicity (may change with time)/state of knowledge of VUS

ETHICAL AND LEGAL ISSUESCountry-specific framework approval?Signed Consent Forms (autonomy protection) (PROSPECTIVE)?Capacity of an individual to consent for submission of the family pedigree data?Anonymisation (privacy protection) vs. medical and scientific interest?

ETHNIC QUALIFICATIONSShould they be population definitions or geographical locations? Founder effects?

INTELLECTUAL PROPERTY RIGHTSHow to protect curators and submitters against misuse?Need to define clarity of data use policy with respect to diagnostic vs. research?

LINKS WITH INDUSTRY AND PRIVATE LABSConditions of access and commercialisation

Database name

URL resource

Contact information (e-mail)

Date resource established

Conditions of use (free or type of license)

Curation policy and curator’s identity

Standards used (gene/symbol/chr. location/

link to RefSeq, ontologies, vocabularies)

Data formats

Data accessibility/output options

Data release policy and frequency

Data submission policy

Documentation available

Relevant publications

Tools available

Disclaimer

CORE DESCRIPTION (HVP recommendations already published)

Patient/family ID (anonymous/encrypted)

Sex

Ethnicity/geographic location

Gene/variant/protein

Clinical Phenotype

Case-control (number of affected/unaffected

carriers and controls

Frequency of the variant in the population(s)

Co-segregation with disease

Allelic status (homozygous, heterozygous, hemizygous)

Co-occurring variants

Detection technique and year of testing

Testing coverage (which genes/exons were tested)

Nomenclature

GOVERNANCE and MANAGEMENTOversight roles and responsibilitiesCharter to regulate relationship with third parties?Medical/legal responsibilities?Dispute resolution?Sustainability and funding

STANDARDS COMPLIANCE and DATA EXCHANGEInteraction between Country Nodes and gene/disease-specific databases (LSDBs)

Scope: purposes of the DB and data types captured QMS (quality management system?)Country-specific framework approval obtained Nature and source of financing or funding

CORE DESCRIPTION : additional HVP recommendations to be formulated ?