Genome sequencing is not yet ready to be a first line genetic test in familial dilated cardiomyopathy because it yields little extra information, Australian research shows.
While genome sequencing is as accurate as current multi-gene panel sequencing for detecting DCM genes, its $6000+ price tag may not be justified for the few additional pathogenic gene variants it identifies, according to genomics researchers at Sydney’s Garvan Institute of Medical Research.
In a study of 42 patients with familial DCM, they found genome sequencing identified all 21 of the DCM genes targed by the current panel sequencing genetic tests. Genome sequencing also identified eight other possible gene variants but none of them were clearly causative of DCM.
Two likely pathogenic gene variants were identified, one of which was missed by panel sequencing. And when genome sequencing was used in family members, the yield of pathogenic variants increased to 24 families (57%) compared to 21 families (50%) achieved with panel sequencing.
The study authors said their findings supported genome sequencing as a viable method for genetic testing, with a high accuracy for DCM genes comparable to panel testing.
However the case for genome sequencing to be used as a first line testing method was weakened by the surprisingly low incremental yield.
A first line role for genome sequencing would have to take into account its high cost – more than double that of panel sequencing – they suggested.
However as the price of genome sequencing testing falls, the cost/yield ratio may become more favourable in future, they added.
The turnaround time for genome sequencing was equal to or faster than that of panel sequencing, they noted, and it would also provide ‘ a storehouse of medically relevant information that extends beyond identification of rare disease-causing variants.”
“For example, polygenic risk scores derived from suites of common variants (often in noncoding regions) may predict an individual’ s risk of DCM complications, and pharmacogenomic associations may guide drug selection and doses< they write in Genetics in Medicine.
A position statement from CSANZ state that “the cost and relatively low yield (~20%) of screening known disease genes has limited the role of genetic testing for DCM patients in routine clinical practice.’
It notes that selective testing of DCM genes is recommended in international guidelines, as well as cascade testing of relatives in families in which a likely disease-causing variant is identified in the index case.
Currently the initial genetic test for DCM costs around $1900 and it not rebated by Medicare.