If one includes histopathologic with clinical findings in defining the affected phenotype, in no other TGFBI corneal dystrophy is the genotype-phenotype correlation as invariant as with combined granular-lattice corneal dystrophy. Dystrophic corneal stromal amyloid deposition is most commonly associated with the p.Arg124Cys mutation in the TGFBI gene, which defines the classic form of lattice corneal dystrophy. However, 26 other mutations in TGFBI have also been associated with variants of the lattice corneal dystrophy phenotype,3- 5,7- 39 18 of which have been confirmed histopathologically to be associated with stromal amyloid deposition.5,9,13,15,17,19,21- 23,25,26,29- 32,34,36,38- 40 Similarly, dystrophic stromal hyaline deposition in the absence of amyloid deposition is most commonly associated with the p.Arg555Trp mutation in the TGFBI gene, which defines the classic form of granular corneal dystrophy. However, 3 other mutations in TGFBI have been associated with variants of the granular corneal dystrophy phenotype,24- 26,37,41,422 of which have been confirmed histopathologically to be associated with stromal hyaline deposition.24,25,37 In each of the 25 families reported to date in which histopathologic examination demonstrated corneal stromal amyloid and hyaline deposition and TGFBI screening has been performed, the p.Arg124His mutation has been identified.25,34,43- 47 None of the other 34 reported mutations in TGFBI have been associated with corneal stromal amyloid and hyaline deposition, suggesting that the nature and location of the p.Arg124His mutation has a unique effect on the structure and function of the TGFBI protein (TGFBIp). Against the backdrop of this invariant phenotype-genotype relationship, we present a family with an atypical variant of lattice corneal dystrophy associated with a novel missense mutation in TGFBI, p.Met619Lys. The distinct clinical phenotype in several affected members, suggestive of an uncommon or novel underlying mutation, was confirmed to be associated with a novel TGFBI mutation through screening of the proband and affected and unaffected family members. However, the demonstration of both amyloid and hyaline deposits on histopathologic examination of several affected individuals violates the previously absolute phenotype-genotype correlation that had existed for combined granular-lattice corneal dystrophy. Thus, this article highlights that clinical and histopathologic features alone cannot be relied on to accurately diagnose and categorize the corneal dystrophies.