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| Mendeliome v1.3176 | MT-ND4L | Zornitza Stark Marked gene: MT-ND4L as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3176 | MT-ND4L | Zornitza Stark Gene: mt-nd4l has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3176 | MT-ND4L | Zornitza Stark Classified gene: MT-ND4L as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3176 | MT-ND4L | Zornitza Stark Gene: mt-nd4l has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3175 | MT-ND4L |
Zornitza Stark gene: MT-ND4L was added gene: MT-ND4L was added to Mendeliome. Sources: Expert list mtDNA tags were added to gene: MT-ND4L. Mode of inheritance for gene gene: MT-ND4L was set to MITOCHONDRIAL Publications for gene: MT-ND4L were set to 8680405; 11935318; 17003408; 22879922; 24568867 Phenotypes for gene: MT-ND4L were set to Mitochondrial disease (MONDO:0044970), MT-ND4L-related Review for gene: MT-ND4L was set to AMBER Added comment: LIMITED by ClinGen. Seven probands with m.10063T>C have been reported across five publications, all of whom had LHON. These cases were scored with reduced points by ClinGen given the mild impact this variant has been shown to have on complex I function. While three other missense variants (m.10543A>G, m.10591T>G, m.10680G>A) have been reported, the ClinGen Expert Panel agreed there was only sufficient evidence of pathogenicity for the m.10663T>C variant. Cases with m.10680G>A and m.10543A>G and m.10591T>G were reviewed but excluded from scoring due to a lack of compelling functional evidence to support pathogenicity. The m.10543A>G variant has been modeled in E. coli and showed a very mild reduction in NADH dehydrogenase activity (74% of control), which was not sufficient to be included in scoring. Sources: Expert list |
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| Mendeliome v1.3174 | MT-ND4 | Zornitza Stark Marked gene: MT-ND4 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3174 | MT-ND4 | Zornitza Stark Gene: mt-nd4 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3174 | MT-ND4 | Zornitza Stark Classified gene: MT-ND4 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3174 | MT-ND4 | Zornitza Stark Gene: mt-nd4 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3173 | MT-ND4 |
Zornitza Stark gene: MT-ND4 was added gene: MT-ND4 was added to Mendeliome. Sources: Expert list mtDNA tags were added to gene: MT-ND4. Mode of inheritance for gene gene: MT-ND4 was set to MITOCHONDRIAL Publications for gene: MT-ND4 were set to 12707444; 16120329; 15576045; 20502985; 27761019; 32445240; 32659360; 3201231 Phenotypes for gene: MT-ND4 were set to Mitochondrial disease (MONDO:0044970), MT-ND4-related Review for gene: MT-ND4 was set to GREEN Added comment: DEFINITIVE by ClinGen. Multiple individuals reported presenting with a broad phenotypic spectrum of clinical features including Leber Hereditary Optic Neuropathy (LHON); mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS); LSS; cerebellar ataxia, migraines, regression, developmental delay, leukoencephalopathy, myoclonus, seizures, stroke-like episodes, cognitive decline, psychiatric illness, Parkinsonism, axonal neuropathy, multiple sclerosis, ophthalmoplegia, short stature, and hypertrophic cardiomyopathy. Age of onset varied from infancy to adulthood. Muscle biopsy showed COX-negative fibers and complex I deficiency. Heteroplasmy levels in affected individuals ranged from 60% - 83% in muscle, 40% - 80% in blood, and 76% - 78% in myoblasts, as well as from 57% - 73% in various other tissues (fibroblasts, liver, urine, buccal). Of note, the m.11778G>A common LHON variant was reported in affected individuals in the homoplasmic and heteroplasmic states. Sources: Expert list |
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