NEW YORK — The American College of Medical Genetics and Genomics has added five genes to its list that it recommends clinical labs report secondary findings on when conducting clinical exome or genome sequencing.
The ACMG first issued such a list in 2013. At that time, it recommended that clinical labs, in addition to reporting findings related to why individuals were undergoing sequencing analysis, also report out results found in a set of 56 genes. This included genes involved in hereditary breast and ovarian cancer, hypertrophic and dilated cardiomyopathy, familial hypercholesterolemia, and more. The ACMG further updated this list in 2016 and 2021, both removing and adding genes.
With the addition of these five new genes — TNNC1, RBM20, BAG3, DES, and TTR — the ACMG version 3.1 list now includes 78 genes. Pathogenic or likely pathogenic variants in the newly added genes contribute to risk of dilated cardiomyopathy or heart failure.
"The v3.1 list is the first of our ongoing yearly updates and embodies our working group's goals of maintaining a minimum list of actionable results that will impact patients and their families in a positive way," David Miller, lead author and co-chair of the ACMG Secondary Findings Working Group, said in a statement.
A paper describing the decision-making process appeared on Friday in Genetics in Medicine.
Pathogenic or likely pathogenic variants in four of the new genes, TNNC1, RBM20, BAG3, and DES, are associated with a predisposition to dilated cardiomyopathy.
The working group noted that other cardiovascular genes are already included on the ACMG list, particularly as they are associated with high risk of heart failure and sudden cardiac risk but also because they are actionable, as some cardiovascular conditions can be treated with medications or implanted defibrillators. For these new genes, the working group determined that the potential benefit of intervention warranted their inclusion on the list.
Meanwhile, pathogenic or likely pathogenic variants in the fifth gene, TTR, are associated with an increased risk of heart failure. The most common pathogenic variant in this gene — p.Val142Ile — has a frequency of between 1 percent and 2.5 percent among individuals of West African ancestry.
The working group considers frequency as one of its criteria for including genes on the secondary findings list and here, even though the variant has a low frequency among the broader US population, they chose to include it because of its effect on a specific US population that is also underrepresented in genomic research.
The working group additionally considered three other genes associated with cancer risk for inclusion on their list, but opted not to at this time, in part due to limited penetrance data or a reported moderate penetrance.
The working group plans to revisit its gene list yearly, updating it in January.