COL11A1 has the largest proportion of splice-site pathogenic variants when compared to all other deafness-associated genes. The majority of these variants are located in the triple-helical domain and cause inframe exon skipping rather than frameshifts. The mutant proteins exert their effect through a dominant-negative mechanism to cause Marshall syndrome (MRSHS) and Stickler syndrome type II (STL2).52, 53 However, biallelic null alleles cause fibrochondrogenesis (FBCG1), a severe recessive often neonatally lethal disease.54 This genotype-phenotype correlation explains the enrichement of splice-altering disease variants in COL11A1.