Course: Interpreting Genomic Variation: Overcoming Challenges in Diverse Populations

Understanding the functional role of an amino acid within a protein and the necessary physicochemical characteristics for that function can help to interpret the probability that a variant will alter …

Changing an amino acid side chain in a protein will change its shape and chemistry which may have functional consequences. Each amino acid has an individual role based on the …

Mendelian inheritance patterns The current variant classification recommends interpreting the variant pathogenicity with respect to a condition and its inheritance pattern. This means the c.1521-1523delCTT (p.Phe508del) variant in the CFTR …

The increased prevalence of a variant in affected individuals (case-cohort) compared to unaffected individuals (control cohort) can provide evidence for a variant being pathogenic, and vice-versa. In the ACMG/AMP classification …

Introduction The first stage in interpreting genomic variation is to predict a variant’s impact on functional elements in the genome (e.g. for your transcript of interest, does the variant lead …

The value of the human genome to society depends on our ability to interpret its sequence, and especially to elucidate its gene content. Since the first human reference genome was …

The first ‘reference’ human genome sequence (i.e. an official assembly), was released over twenty years ago, produced as part of the Human Genome Project (HGP). This first assembly was a …

What is a genomic database of variants? A genomic database is a structured set of variants held in a computer database and can be accessed in several ways, most often …

The goal of medical evaluation is to make a diagnosis. To achieve this we need to explore medical histories, evaluate the symptoms of a condition and perform relevant diagnostic tests. …

Up-to-date knowledge on the association of genes with specific phenotypes or diseases is of great importance in variant interpretation, as it enables variants predicted to affect the function of known …

ACMG/AMP guidelines The current guidelines for variant classification and interpretation stem from the expert opinion of the workgroup convened by the American College of Medical Genetics and Genomics (ACMG) in …

When a change occurs in the genome, it could have an impact on the function of the cell and in some cases can even lead to disease. Genomic variant interpretation …

Research informs variant interpretation. The tools and data resources used for variant interpretation are all developed from research endeavours that involve rare disease patients. These participants offer their clinical information …

In this video, learn from Dr Julia Foreman how to interpret sequence variants using DECIPHER. You will watch a tutorial for two examples showing how to use DECIPHER to identify …

Dr Mohnish Suri, from Nottingham University Hospitals, discusses in this interview the importance of phenotyping for variant interpretation in genomic tests. Phenotyping helps establish a causal link between variants and …