MT-TI is a mitochondrial gene that encodes for mitochondrially-encoded tRNA for isoleucine, it is located on the heavy stand of mitochondrial DNA spanning 69 nucleotides 4263-4331. MT-TI was first reported in association with hypertrophic cardiomyopathy in 1996 (Merante et al. 1996, PMID: 8889580). Three variants have been seen in five probands in three publications (PMIDs: 8889580, 12767666, 37124643). One homoplastic variant m.4300A>G is seen in most cases, including in a family segregating to 16 affected family members. Each variant has supporting histochemical and biochemical functional evidence from patient biopsies. This gene-disease relationship is also supported by expression studies (PMID: 8889580, 34265302). In summary, there is MODERATE evidence supporting the relationship between MT-TI and hypertrophic cardiomyopathy. The ClinGen Hereditary Cardiovascular Disease GCEP approved this classification on the meeting date December 18, 2023.
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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