ClinVar

Description

The p.T80I variant (also known as c.239C>T), located in coding exon 3 of the TTR gene, results from a C to T substitution at nucleotide position 239. The threonine at codon 80 is replaced by isoleucine, an amino acid with similar properties. This alteration has been reported in multiple patients with transthyretin (ATTR) amyloidosis (Ambry internal data; external communication; Chaudhary AG et al. CJC Open, 2022 Dec;4:1031-1035). This variant was also described in a Saudi exome cohort; however, clinical details were limited (Abouelhoda M et al. Hum Genomics, 2021 Aug;15:52). An alternate amino acid substitution at this position, p.T80A (historically described as p.T60A), has been detected in numerous individuals with ATTR amyloidosis and is associated with cardiac symptoms (Wallace MR et al. J. Clin. Invest., 1986 Jul;78:6-12; Zeldenrust SR. Amyloid, 2012 Jun;19 Suppl 1:22-4; Ihse E et al. Amyloid, 2013 Sep;20:142-50; Swiecicki PL et al. Amyloid, 2015 May;22:123-31). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.