When Silence Disrupts
RC Hunt et al, NEJM, August 24, 2022
A common assumption is that synonymous codon changes, so called because they do not alter the encoded amino acid sequence, are neutral genetic variants that have no effect on phenotype or genetic fitness. However, there is a mounting body of literature showing that synonymous variants influence protein biosynthesis and the biologic behavior of cells and underlie human disease.
Genomic tools for health: Secondary findings as findings to be shared
SA Miner et al, Genetics in Medicine, August 18, 2022
To explore how parents understand SF disclosure in the context of their child and other family members’ lives, we conducted semistructured interviews with 30 families (40 parents in total). All parents had children who were enrolled in a genetic sequencing protocol that returned results by default. We found that parents did not routinely conceptualize SFs as distinctive health information. Rather parents saw this information as part of their child’s overall health. To make decisions about disclosure, parents weighed their child’s ability to understand the SF information and their other family member’s need to know.
ACMG SF v3.1 list for reporting of secondary findings in clinical exome and genome sequencing: A policy statement of the American College of Medical Genetics and Genomics (ACMG)
DT Miller et al, Genetics in Medicine, June 17, 2022
In total, 5 new genes were added to the v3.1 list, with a brief description of the factors considered in adding these genes. A list of 3 genes considered for inclusion, but ultimately excluded from the v3.1 list; these genes could be reviewed again in the future if new data emerge. TTR (transthyretin) was previously reviewed by the SFWG for TTR-associated amyloidosis and not included on the SF v3.0 list. However, this gene–phenotype pair was reconsidered and included in SF v3.1 because of the availability of new data on population prevalence and US Food and Drug Administration–approved treatments, demonstrating the fluidity of the SF list over time as new information emerges.
ORCA, a values-based decision aid for selecting additional findings from genomic sequencing in adults: Efficacy results from a randomized trial.
Liles Elizabeth G et al. Genetics in medicine : official journal of the American College of Medical Genetics 2022 5
Individuals having genomic sequencing can choose to be notified about pathogenic variants in genes unrelated to the testing indication. A decision aid can facilitate weighing one's values before making a choice about these additional results. We conducted a randomized trial (N = 231) comparing informed values-choice congruence among adults at risk for a hereditary cancer syndrome who viewed either the Optional Results Choice Aid (ORCA) or web-based additional findings information alone. ORCA is values-focused with a low-literacy design. The ORCA decision aid did not significantly improve informed values-choice congruence over web-based information in this cohort of adults deciding about genomic results. Both web-based approaches may be effective for adults to decide about receiving medically actionable additional results.