Table 5.

Criteria Used to Decide Relevancy for Return of Results for Rare Variants in DCM Genetic Research

	Established DCM Gene	Novel DCM Gene
Variant previously published as disease causing	x	NAa
Rare	x	x
Nucleotide and/or amino acid conserved across species	x	x
Type of variant (.e.g, nonsynonymous, nonsense, splice site, etc)	x	x
Familial segregation	x	x
Multiple rare variants associated with disease, ideally segregating in more than one family		x
Relevant functional data	xb	x
Histological evidence of key protein/protein disruption in human tissue specimens		x

^aNA is not applicable.

^bThe availability of functional data for specific variants identified in established DCM genes adds to certainty, especially for novel variants in sporadic disease, as discerning pathologic versus neutral variants can be challenging without evidence of segregation.