After Bonferroni correction for multiple hypothesis testing, a single subnetwork from the AVSD trios composed of a pair of interacting collagen genes (COL2A1, COL9A1) (Fig 4a and 4c) displayed an elevated burden of rare coding variation in 100 affected individuals with AVSD compared to 533 controls without congenital heart disease (p = 8.37e-08, SKAT linear weighted test) (Fig 4c). Here, COL2A1 is linked to congenital heart disease.