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| Mitochondrial disease v0.1275 | MT-TC |
Zornitza Stark changed review comment from: LIMITED by ClinGen. There were 3 scoreable probands across >10 publications from 1996-2022. Notably, while cybrid analyses were performed (PMID:36039763), one of the variants, m.5783G>A, was excluded from scoring for three reasons: 1.) the reported phenotype of isolated hearing loss was non-specific and incompletely penetrant, but also 2.) the biochemical impact in cybrids was mild - moderate, and 3.) there was reduction in expression of mitochondrial replication genes (TWNK ~30% of control in cybrids) suggesting an alternative aetiology might be responsible for the biochemical impact reported. The gene-disease association for MT-TC is also supported by the known interaction with a multitude of other mitochondrial translation proteins (PMID:30030363) and respiratory chain studies and Northern blot analysis supporting MT-TC dysfunction leading to Complex I deficiency (PMID:35252560).; to: LIMITED by ClinGen. There were 3 scoreable probands across >10 publications from 1996-2022. Notably, while cybrid analyses were performed (PMID:36039763), one of the variants, m.5783G>A, was excluded from scoring for three reasons: 1.) the reported phenotype of isolated hearing loss was non-specific and incompletely penetrant, but also 2.) the biochemical impact in cybrids was mild - moderate, and 3.) there was reduction in expression of mitochondrial replication genes (TWNK ~30% of control in cybrids) suggesting an alternative aetiology might be responsible for the biochemical impact reported. Reported phenotypes are variable but include dystonia, neuropathy, myoclonic epilepsy, ataxia, retinitis pigmentosa, and muscle weakness. The gene-disease association for MT-TC is also supported by the known interaction with a multitude of other mitochondrial translation proteins (PMID:30030363) and respiratory chain studies and Northern blot analysis supporting MT-TC dysfunction leading to Complex I deficiency (PMID:35252560). |
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| Mitochondrial disease v0.1040 | MT-TC | Zornitza Stark Publications for gene: MT-TC were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mitochondrial disease v0.1039 | MT-TC | Zornitza Stark Phenotypes for gene: MT-TC were changed from MELAS; Dystonia to Mitochondrial disease (MONDO:0044970), MT-TC-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mitochondrial disease v0.1038 | MT-TC | Zornitza Stark Classified gene: MT-TC as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mitochondrial disease v0.1038 | MT-TC | Zornitza Stark Gene: mt-tc has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mitochondrial disease v0.1037 | MT-TC |
Zornitza Stark edited their review of gene: MT-TC: Added comment: LIMITED by ClinGen. There were 3 scoreable probands across >10 publications from 1996-2022. Notably, while cybrid analyses were performed (PMID:36039763), one of the variants, m.5783G>A, was excluded from scoring for three reasons: 1.) the reported phenotype of isolated hearing loss was non-specific and incompletely penetrant, but also 2.) the biochemical impact in cybrids was mild - moderate, and 3.) there was reduction in expression of mitochondrial replication genes (TWNK ~30% of control in cybrids) suggesting an alternative aetiology might be responsible for the biochemical impact reported. The gene-disease association for MT-TC is also supported by the known interaction with a multitude of other mitochondrial translation proteins (PMID:30030363) and respiratory chain studies and Northern blot analysis supporting MT-TC dysfunction leading to Complex I deficiency (PMID:35252560).; Changed rating: AMBER; Changed publications: 8829635, 9185178, 17241783, 11453453, 16955414, 32169613, 36039763, 17724295, 35252560, 34433719, 30030363; Changed phenotypes: Mitochondrial disease (MONDO:0044970), MT-TC-related |
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| Mitochondrial disease v0.430 | MT-TC | Zornitza Stark Tag mtDNA tag was added to gene: MT-TC. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mitochondrial disease v0.391 | MT-TC | Zornitza Stark Marked gene: MT-TC as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mitochondrial disease v0.391 | MT-TC | Zornitza Stark Gene: mt-tc has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mitochondrial disease v0.391 | MT-TC | Zornitza Stark Classified gene: MT-TC as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mitochondrial disease v0.391 | MT-TC | Zornitza Stark Gene: mt-tc has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mitochondrial disease v0.390 | MT-TC |
Zornitza Stark gene: MT-TC was added gene: MT-TC was added to Mitochondrial disease. Sources: Expert list Mode of inheritance for gene gene: MT-TC was set to MITOCHONDRIAL Phenotypes for gene: MT-TC were set to MELAS; Dystonia Review for gene: MT-TC was set to GREEN Added comment: Sources: Expert list |
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