ClinVar

Description

The p.D38E pathogenic mutation (also known as c.114T>A), located in coding exon 2 of the TTR gene, results from a T to A substitution at nucleotide position 114. The aspartic acid at codon 38 is replaced by glutamic acid, an amino acid with highly similar properties. This variant (also referred to as D18E) was reported to cause complete absence of protein when analyzed by electrophoresis detection method (Atland et al 2007. Electrophoresis 2007 Jun;28(12):2053-64). A patient presenting with cardiomyopathy due to amyloid deposits was reported with this pathogenic mutation (Connors LH et al. Amyloid 2004; 11:61-6). This mutation was further described in a patient who presented with vitreous deposits of amyloid and a significant family history of amyloidosis who developed further amyloid deposits and required a heart/kidney/liver transplant (Solano JM et al. Ophthalmic Genet. 2007; 28:73-5). Other alterations at the same codon, including p.D38N (c.112G>A), have also been reported in association with amyloidosis (Quarta CC & Falk RH. Amyloid. 2012;19(4):204-7). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.