{"count":220751,"next":"https://panelapp-aus.org/api/v1/activities/?format=json&page=162","previous":"https://panelapp-aus.org/api/v1/activities/?format=json&page=160","results":[{"created":"2025-09-29T16:26:10.183668+10:00","panel_name":"Mitochondrial disease","panel_id":203,"panel_version":"0.1046","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: MT-TG: Added comment: MODERATE by ClinGen.\r\n\r\nFour variants reported in at least 6 individuals. Age of onset in affected individuals varied from early in life to the 20s. Clinical features included hypertrophic cardiomyopathy, myopathy, peripheral neuropathy, exercise intolerance, headache, seizures, ataxia, dystonic posturing, optic atrophy, retinal dystrophy, cataracts, and hearing loss. Progressive atrophy and bilateral basal ganglia calcifications were seen on brain imaging.\r\n\r\nTissue biopsies identified ragged red fibers and decreased COX histochemical activity in muscle. Lab values showed increased blood lactate and increased creatine kinase. Decreased activities of complexes I, III, and IV were observed in biopsied muscle.\r\n\r\nHeteroplasmy levels of the variants in affected individuals ranged from 88-92% in muscle, 40-56% in urine, undetectable to 32% in blood, 27% in buccal samples, and was undetectable when assessed in fibroblasts. Single fiber testing and cybrid analysis further supported variant pathogenicity. This gene-disease relationship is also supported by known biochemical function and functional alterations in patient cells (in vitro functional assays demonstrated reduced rates of mitochondrial translation as a result of variants in MT-TG; PMID: 10090480).; Changed publications: 8079988, 9199564, 11971101, 16120360, 32337339, 35432167, 10090480; Changed phenotypes: Mitochondrial disease (MONDO:0044970), MT-TG-related","entity_name":"MT-TG","entity_type":"gene"},{"created":"2025-09-29T16:25:52.097203+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3195","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: MT-TG as ready","entity_name":"MT-TG","entity_type":"gene"},{"created":"2025-09-29T16:25:52.090191+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3195","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: mt-tg has been classified as Green List (High Evidence).","entity_name":"MT-TG","entity_type":"gene"},{"created":"2025-09-29T16:25:36.795774+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3195","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: MT-TG as Green List (high evidence)","entity_name":"MT-TG","entity_type":"gene"},{"created":"2025-09-29T16:25:36.787699+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3195","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: mt-tg has been classified as Green List (High Evidence).","entity_name":"MT-TG","entity_type":"gene"},{"created":"2025-09-29T16:25:21.193951+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3194","user_name":"Zornitza Stark","item_type":"entity","text":"Tag mtDNA tag was added to gene: MT-TG.","entity_name":"MT-TG","entity_type":"gene"},{"created":"2025-09-29T16:25:08.895579+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3194","user_name":"Zornitza Stark","item_type":"entity","text":"gene: MT-TG was added\ngene: MT-TG was added to Mendeliome. Sources: Expert list\nMode of inheritance for gene gene: MT-TG was set to MITOCHONDRIAL\nPublications for gene: MT-TG were set to 8079988; 9199564; 11971101; 16120360; 32337339; 35432167; 10090480\nPhenotypes for gene: MT-TG were set to Mitochondrial disease (MONDO:0044970), MT-TG-related\nReview for gene: MT-TG was set to GREEN\nAdded comment: MODERATE by ClinGen.\r\n\r\nFour variants reported in at least 6 individuals. Age of onset in affected individuals varied from early in life to the 20s. Clinical features included hypertrophic cardiomyopathy, myopathy, peripheral neuropathy, exercise intolerance, headache, seizures, ataxia, dystonic posturing, optic atrophy, retinal dystrophy, cataracts, and hearing loss. Progressive atrophy and bilateral basal ganglia calcifications were seen on brain imaging.\r\n\r\nTissue biopsies identified ragged red fibers and decreased COX histochemical activity in muscle. Lab values showed increased blood lactate and increased creatine kinase. Decreased activities of complexes I, III, and IV were observed in biopsied muscle.\r\n\r\nHeteroplasmy levels of the variants in affected individuals ranged from 88-92% in muscle, 40-56% in urine, undetectable to 32% in blood, 27% in buccal samples, and was undetectable when assessed in fibroblasts. Single fiber testing and cybrid analysis further supported variant pathogenicity. This gene-disease relationship is also supported by known biochemical function and functional alterations in patient cells (in vitro functional assays demonstrated reduced rates of mitochondrial translation as a result of variants in MT-TG; PMID: 10090480). \nSources: Expert list","entity_name":"MT-TG","entity_type":"gene"},{"created":"2025-09-29T16:22:07.363870+10:00","panel_name":"Mitochondrial disease","panel_id":203,"panel_version":"0.1046","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: MT-TF were changed from MELAS; MERFF; Encephalopathy; Myopathy to Mitochondrial disease (MONDO:0044970), MT-TF-related","entity_name":"MT-TF","entity_type":"gene"},{"created":"2025-09-29T16:21:41.516744+10:00","panel_name":"Mitochondrial disease","panel_id":203,"panel_version":"0.1045","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: MT-TF were set to ","entity_name":"MT-TF","entity_type":"gene"},{"created":"2025-09-29T16:21:12.899069+10:00","panel_name":"Mitochondrial disease","panel_id":203,"panel_version":"0.1044","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: MT-TF: Added comment: DEFINITIVE by ClinGen.\r\n\r\nOver 30 individuals reported. Age of onset in affected individuals varied from childhood to >60 years. Clinical features in affected individuals included mitochondrial myopathy, MELAS, myoclonic epilepsy and ragged red fibers (MERRF), chronic external progressive ophthalmoplegia (CPEO), Gitelman syndrome, epilepsy, epilepsia partialis continua (EPC), chronic kidney disease, retinal dystrophy, sensorineural hearing loss, neuropathy, and neurologic/cognitive/psychiatric decline. Some affected individuals had normal brain imaging while others had cerebral, cerebellar, and/or brainstem atrophy.\r\n\r\nMuscle biopsies showed ragged red fibers, COX-negative fibers, and decreased respiratory chain enzyme activities in some cases, although activities were normal in other individuals. Laboratory investigations showed variable lactate levels (normal to elevated in blood, cerebrospinal fluid, and/or urine) and elevated creatine kinase (CK).\r\n\r\nHeteroplasmy levels in affected individuals were highest in muscle when multiple tissues were assessed, and ranged from 58%-homoplasmic in muscle; 0-70% in hair, 0-homoplasmic in blood, fibroblast, and urine; and in one individual was 63% in a buccal sample.; Changed publications: 14659412, 9771776, 16806928, 21060018, 31463198, 32419253, 34607911, 21424749, 15184630, 20142618, 28267784, 31722346, 35472031, 9636664, 21882289, 16769874, 21914246, 31009750, 18977334; Changed phenotypes: Mitochondrial disease (MONDO:0044970), MT-TF-related","entity_name":"MT-TF","entity_type":"gene"},{"created":"2025-09-29T16:20:39.877185+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3193","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: MT-TF: Changed phenotypes: Mitochondrial disease (MONDO:0044970), MT-TF-related","entity_name":"MT-TF","entity_type":"gene"},{"created":"2025-09-29T16:20:28.113428+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3193","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: MT-TF as ready","entity_name":"MT-TF","entity_type":"gene"},{"created":"2025-09-29T16:20:28.103282+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3193","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: mt-tf has been classified as Green List (High Evidence).","entity_name":"MT-TF","entity_type":"gene"},{"created":"2025-09-29T16:20:21.010852+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3193","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: MT-TF were changed from Mitochondrial disease (MONDO:0044970), MT-TF-relatedn to Mitochondrial disease (MONDO:0044970), MT-TF-related","entity_name":"MT-TF","entity_type":"gene"},{"created":"2025-09-29T16:20:03.029954+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3192","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: MT-TF as Green List (high evidence)","entity_name":"MT-TF","entity_type":"gene"},{"created":"2025-09-29T16:20:03.021941+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3192","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: mt-tf has been classified as Green List (High Evidence).","entity_name":"MT-TF","entity_type":"gene"},{"created":"2025-09-29T16:19:52.006383+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3191","user_name":"Zornitza Stark","item_type":"entity","text":"Tag mtDNA tag was added to gene: MT-TF.","entity_name":"MT-TF","entity_type":"gene"},{"created":"2025-09-29T16:19:40.806264+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3191","user_name":"Zornitza Stark","item_type":"entity","text":"gene: MT-TF was added\ngene: MT-TF was added to Mendeliome. Sources: Expert list\nMode of inheritance for gene gene: MT-TF was set to MITOCHONDRIAL\nPublications for gene: MT-TF were set to 14659412; 9771776; 16806928; 21060018; 31463198; 32419253; 34607911; 21424749; 15184630; 20142618; 28267784; 31722346; 35472031; 9636664; 21882289; 16769874; 21914246; 31009750; 18977334\nPhenotypes for gene: MT-TF were set to Mitochondrial disease (MONDO:0044970), MT-TF-relatedn\nReview for gene: MT-TF was set to GREEN\nAdded comment: DEFINITIVE by ClinGen.\r\n\r\nOver 30 individuals reported. Age of onset in affected individuals varied from childhood to >60 years. Clinical features in affected individuals included mitochondrial myopathy, MELAS, myoclonic epilepsy and ragged red fibers (MERRF), chronic external progressive ophthalmoplegia (CPEO), Gitelman syndrome, epilepsy, epilepsia partialis continua (EPC), chronic kidney disease, retinal dystrophy, sensorineural hearing loss, neuropathy, and neurologic/cognitive/psychiatric decline. Some affected individuals had normal brain imaging while others had cerebral, cerebellar, and/or brainstem atrophy.\r\n\r\nMuscle biopsies showed ragged red fibers, COX-negative fibers, and decreased respiratory chain enzyme activities in some cases, although activities were normal in other individuals. Laboratory investigations showed variable lactate levels (normal to elevated in blood, cerebrospinal fluid, and/or urine) and elevated creatine kinase (CK).\r\n\r\nHeteroplasmy levels in affected individuals were highest in muscle when multiple tissues were assessed, and ranged from 58%-homoplasmic in muscle; 0-70% in hair, 0-homoplasmic in blood, fibroblast, and urine; and in one individual was 63% in a buccal sample. \nSources: Expert list","entity_name":"MT-TF","entity_type":"gene"},{"created":"2025-09-29T16:16:04.047953+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3190","user_name":"Zornitza Stark","item_type":"entity","text":"Tag mtDNA tag was added to gene: MT-TE.","entity_name":"MT-TE","entity_type":"gene"},{"created":"2025-09-29T16:15:49.984222+10:00","panel_name":"Mitochondrial disease","panel_id":203,"panel_version":"0.1044","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: MT-TE were changed from Mitochondrial myopathy; Deafness; Diabetes to Mitochondrial disease (MONDO:0044970), MT-TE-related","entity_name":"MT-TE","entity_type":"gene"},{"created":"2025-09-29T16:15:24.442227+10:00","panel_name":"Mitochondrial disease","panel_id":203,"panel_version":"0.1043","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: MT-TE were set to ","entity_name":"MT-TE","entity_type":"gene"},{"created":"2025-09-29T16:14:52.032359+10:00","panel_name":"Mitochondrial disease","panel_id":203,"panel_version":"0.1042","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: MT-TE: Added comment: DEFINITIVE by ClinGen.\r\n\r\nMore than 15 individuals reported. Age of onset in affected individuals varied from birth to 30s. Clinical features in affected individuals included (benign) infantile reversible COX deficiency myopathy (also referred to RIRCD); chronic external progressive ophthalmoplegia (CPEO), mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS)/Leigh syndrome spectrum overlap, myoclonic epilepsy and ragged red fibers (MERRF); pigmentary retinopathy, migraines, myopathy, diabetes, pulmonary hypertension, ataxia, neuropathy, global developmental delay, dysarthria, and hearing loss. Brain imaging was variable. Muscle biopsies showed ragged red fibers, COX-negative fibers, and decreased respiratory chain enzyme activities in some cases, although activities were normal in other individuals.\r\n\r\nHeteroplasmy levels in affected individuals were highest in muscle when multiple tissues were assessed, and were variable in other tissues when tested.; Changed publications: 8155739, 21194154, 17715279, 23334599, 7726155, 7726154, 9353617, 15048886, 15670724, 23847141, 23334599, 17266923, 17056256; Changed phenotypes: Mitochondrial disease (MONDO:0044970), MT-TE-related","entity_name":"MT-TE","entity_type":"gene"},{"created":"2025-09-29T16:14:36.548885+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3190","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: MT-TE as ready","entity_name":"MT-TE","entity_type":"gene"},{"created":"2025-09-29T16:14:36.538578+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3190","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: mt-te has been classified as Green List (High Evidence).","entity_name":"MT-TE","entity_type":"gene"},{"created":"2025-09-29T16:14:05.299422+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3190","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: MT-TE as Green List (high evidence)","entity_name":"MT-TE","entity_type":"gene"},{"created":"2025-09-29T16:14:05.287783+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3190","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: mt-te has been classified as Green List (High Evidence).","entity_name":"MT-TE","entity_type":"gene"},{"created":"2025-09-29T16:13:48.389808+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3189","user_name":"Zornitza Stark","item_type":"entity","text":"gene: MT-TE was added\ngene: MT-TE was added to Mendeliome. Sources: Expert list\nMode of inheritance for gene gene: MT-TE was set to MITOCHONDRIAL\nPublications for gene: MT-TE were set to 8155739; 21194154; 17715279; 23334599; 7726155; 7726154; 9353617; 15048886; 15670724; 23847141; 23334599; 17266923; 17056256\nPhenotypes for gene: MT-TE were set to Mitochondrial disease (MONDO:0044970), MT-TE-related\nReview for gene: MT-TE was set to GREEN\nAdded comment: DEFINITIVE by ClinGen.\r\n\r\nMore than 15 individuals reported. Age of onset in affected individuals varied from birth to 30s. Clinical features in affected individuals included (benign) infantile reversible COX deficiency myopathy (also referred to RIRCD); chronic external progressive ophthalmoplegia (CPEO), mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS)/Leigh syndrome spectrum overlap, myoclonic epilepsy and ragged red fibers (MERRF); pigmentary retinopathy, migraines, myopathy, diabetes, pulmonary hypertension, ataxia, neuropathy, global developmental delay, dysarthria, and hearing loss. Brain imaging was variable. Muscle biopsies showed ragged red fibers, COX-negative fibers, and decreased respiratory chain enzyme activities in some cases, although activities were normal in other individuals.\r\n\r\nHeteroplasmy levels in affected individuals were highest in muscle when multiple tissues were assessed, and were variable in other tissues when tested. \nSources: Expert list","entity_name":"MT-TE","entity_type":"gene"},{"created":"2025-09-29T16:10:38.446055+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3188","user_name":"Zornitza Stark","item_type":"entity","text":"Tag mtDNA tag was added to gene: MT-TD.","entity_name":"MT-TD","entity_type":"gene"},{"created":"2025-09-29T16:09:58.799035+10:00","panel_name":"Mitochondrial disease","panel_id":203,"panel_version":"0.1042","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: MT-TD were changed from Mitochondrial myopathy to Mitochondrial disease (MONDO:0044970), MT-TD-related","entity_name":"MT-TD","entity_type":"gene"},{"created":"2025-09-29T16:09:14.861700+10:00","panel_name":"Mitochondrial disease","panel_id":203,"panel_version":"0.1041","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: MT-TD were set to ","entity_name":"MT-TD","entity_type":"gene"},{"created":"2025-09-29T16:08:44.254239+10:00","panel_name":"Mitochondrial disease","panel_id":203,"panel_version":"0.1040","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: MT-TD: Added comment: MODERATE by ClinGen.\r\n\r\nAt least 3 variants reported in unrelated individuals. These variants were generally present at high levels of heteroplasmy in muscle tissue and at lower to undetectable levels in other tissues such as blood, saliva, buccal tissue, urine, and fibroblasts, highlighting the diagnostic importance of muscle biopsy in MT-TD-related primary mitochondrial disease. Single fiber studies were performed in several individuals with results supporting variant pathogenicity.\r\n\r\nThis gene-disease association is also supported by functional implication given protein interaction with the multitude of other mitochondrial translation proteins linked to primary mitochondrial disease (PMID: 30030363 ). Respiratory deficient yeast strains due to a single variant in MT-TD have been created and compelling rescue studies have been performed (PMIDs: 7024270, 3054486). E. coli carrying the m.7526A>G variant were also shown to have significantly decreased aminoacylation rates (PMID: 19535463).; Changed publications: 9811342, 10488907, 16059939, 18676632, 23696415, 25447692, 27536005, 30030363, 3054486, 19535463; Changed phenotypes: Mitochondrial disease (MONDO:0044970), MT-TD-related","entity_name":"MT-TD","entity_type":"gene"},{"created":"2025-09-29T16:08:27.164768+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3188","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: MT-TD as ready","entity_name":"MT-TD","entity_type":"gene"},{"created":"2025-09-29T16:08:27.151968+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3188","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: mt-td has been classified as Green List (High Evidence).","entity_name":"MT-TD","entity_type":"gene"},{"created":"2025-09-29T16:08:10.036198+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3188","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: MT-TD as Green List (high evidence)","entity_name":"MT-TD","entity_type":"gene"},{"created":"2025-09-29T16:08:10.026053+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3188","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: mt-td has been classified as Green List (High Evidence).","entity_name":"MT-TD","entity_type":"gene"},{"created":"2025-09-29T16:07:46.965286+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3187","user_name":"Zornitza Stark","item_type":"entity","text":"gene: MT-TD was added\ngene: MT-TD was added to Mendeliome. Sources: Expert list\nMode of inheritance for gene gene: MT-TD was set to MITOCHONDRIAL\nPublications for gene: MT-TD were set to 9811342; 10488907; 16059939; 18676632; 23696415; 25447692; 27536005; 30030363; 3054486; 19535463\nPhenotypes for gene: MT-TD were set to Mitochondrial disease (MONDO:0044970), MT-TD-related\nReview for gene: MT-TD was set to GREEN\nAdded comment: MODERATE by ClinGen.\r\n\r\nAt least 3 variants reported in unrelated individuals. These variants were generally present at high levels of heteroplasmy in muscle tissue and at lower to undetectable levels in other tissues such as blood, saliva, buccal tissue, urine, and fibroblasts, highlighting the diagnostic importance of muscle biopsy in MT-TD-related primary mitochondrial disease. Single fiber studies were performed in several individuals with results supporting variant pathogenicity.\r\n\r\nThis gene-disease association is also supported by functional implication given protein interaction with the multitude of other mitochondrial translation proteins linked to primary mitochondrial disease (PMID: 30030363 ). Respiratory deficient yeast strains due to a single variant in MT-TD have been created and compelling rescue studies have been performed (PMIDs: 7024270, 3054486). E. coli carrying the m.7526A>G variant were also shown to have significantly decreased aminoacylation rates (PMID: 19535463). \nSources: Expert list","entity_name":"MT-TD","entity_type":"gene"},{"created":"2025-09-29T16:03:58.064770+10:00","panel_name":"Mitochondrial disease","panel_id":203,"panel_version":"0.1040","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: MT-TC were set to ","entity_name":"MT-TC","entity_type":"gene"},{"created":"2025-09-29T16:03:35.064373+10:00","panel_name":"Mitochondrial disease","panel_id":203,"panel_version":"0.1039","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: MT-TC were changed from MELAS; Dystonia to Mitochondrial disease (MONDO:0044970), MT-TC-related","entity_name":"MT-TC","entity_type":"gene"},{"created":"2025-09-29T16:03:07.504136+10:00","panel_name":"Mitochondrial disease","panel_id":203,"panel_version":"0.1038","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: MT-TC as Amber List (moderate evidence)","entity_name":"MT-TC","entity_type":"gene"},{"created":"2025-09-29T16:03:07.494252+10:00","panel_name":"Mitochondrial disease","panel_id":203,"panel_version":"0.1038","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: mt-tc has been classified as Amber List (Moderate Evidence).","entity_name":"MT-TC","entity_type":"gene"},{"created":"2025-09-29T16:02:41.519687+10:00","panel_name":"Mitochondrial disease","panel_id":203,"panel_version":"0.1037","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: MT-TC: Added comment: LIMITED by ClinGen.\r\n\r\nThere 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.\r\n\r\nThe 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","entity_name":"MT-TC","entity_type":"gene"},{"created":"2025-09-29T16:02:23.941217+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3186","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: MT-TC as ready","entity_name":"MT-TC","entity_type":"gene"},{"created":"2025-09-29T16:02:23.933217+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3186","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: mt-tc has been classified as Amber List (Moderate Evidence).","entity_name":"MT-TC","entity_type":"gene"},{"created":"2025-09-29T16:01:58.890783+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3186","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: MT-TC as Amber List (moderate evidence)","entity_name":"MT-TC","entity_type":"gene"},{"created":"2025-09-29T16:01:58.883098+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3186","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: mt-tc has been classified as Amber List (Moderate Evidence).","entity_name":"MT-TC","entity_type":"gene"},{"created":"2025-09-29T16:01:42.951794+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3185","user_name":"Zornitza Stark","item_type":"entity","text":"gene: MT-TC was added\ngene: MT-TC was added to Mendeliome. Sources: Expert list\nMode of inheritance for gene gene: MT-TC was set to MITOCHONDRIAL\nPublications for gene: MT-TC were set to 8829635; 9185178; 17241783; 11453453; 16955414; 32169613; 36039763; 17724295; 35252560; 34433719; 30030363\nPhenotypes for gene: MT-TC were set to Mitochondrial disease (MONDO:0044970), MT-TC-related\nReview for gene: MT-TC was set to AMBER\nAdded comment: LIMITED by ClinGen.\r\n\r\nThere 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.\r\n\r\nThe 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). \nSources: Expert list","entity_name":"MT-TC","entity_type":"gene"},{"created":"2025-09-29T15:56:11.415857+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3184","user_name":"Sangavi Sivagnanasundram","item_type":"entity","text":"reviewed gene: NDP: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Norrie disease MONDO:0010691; Mode of inheritance: None","entity_name":"NDP","entity_type":"gene"},{"created":"2025-09-29T15:55:36.837487+10:00","panel_name":"Mitochondrial disease","panel_id":203,"panel_version":"0.1037","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: MT-TA were changed from Mitochondrial myopathy to Mitochondrial disease (MONDO:0044970), MT-TA-related","entity_name":"MT-TA","entity_type":"gene"},{"created":"2025-09-29T15:55:05.409709+10:00","panel_name":"Mitochondrial disease","panel_id":203,"panel_version":"0.1036","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: MT-TA were set to ","entity_name":"MT-TA","entity_type":"gene"},{"created":"2025-09-29T15:54:29.665051+10:00","panel_name":"Mitochondrial disease","panel_id":203,"panel_version":"0.1035","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: MT-TA: Added comment: DEFINITIVE by ClinGen.\r\n\r\nMore than 5 individuals reported. Variable age of onset. Features in affected individuals included myopathy (weakness, exercise intolerance), ptosis, ophthalmoplegia, lipomas, and hearing loss. Muscle biopsies showed ragged red fibers and COX-negative fibers, as well as respiratory chain enzyme deficiencies. Heteroplasmy levels in affected individuals tended to be highest in muscle when multiple tissues were assessed and were variable in other tissues when tested.; Changed publications: 11715067, 17825557, 14569122, 27014581, 20813205, 25873012, 16476954; Changed phenotypes: Mitochondrial disease (MONDO:0044970), MT-TA-related","entity_name":"MT-TA","entity_type":"gene"},{"created":"2025-09-29T15:53:57.123084+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3184","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: MT-TA as ready","entity_name":"MT-TA","entity_type":"gene"},{"created":"2025-09-29T15:53:57.112861+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3184","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: mt-ta has been classified as Green List (High Evidence).","entity_name":"MT-TA","entity_type":"gene"},{"created":"2025-09-29T15:53:47.529289+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3184","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: MT-TA as Green List (high evidence)","entity_name":"MT-TA","entity_type":"gene"},{"created":"2025-09-29T15:53:47.519261+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3184","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: mt-ta has been classified as Green List (High Evidence).","entity_name":"MT-TA","entity_type":"gene"},{"created":"2025-09-29T15:53:26.111360+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3183","user_name":"Zornitza Stark","item_type":"entity","text":"gene: MT-TA was added\ngene: MT-TA was added to Mendeliome. Sources: Expert list\nMode of inheritance for gene gene: MT-TA was set to MITOCHONDRIAL\nPublications for gene: MT-TA were set to 11715067; 17825557; 14569122; 27014581; 20813205; 25873012; 16476954\nPhenotypes for gene: MT-TA were set to Mitochondrial disease (MONDO:0044970), MT-TA-related\nReview for gene: MT-TA was set to GREEN\nAdded comment: DEFINITIVE by ClinGen.\r\n\r\nMore than 5 individuals reported. Variable age of onset. Features in affected individuals included myopathy (weakness, exercise intolerance), ptosis, ophthalmoplegia, lipomas, and hearing loss. Muscle biopsies showed ragged red fibers and COX-negative fibers, as well as respiratory chain enzyme deficiencies. Heteroplasmy levels in affected individuals tended to be highest in muscle when multiple tissues were assessed and were variable in other tissues when tested. \nSources: Expert list","entity_name":"MT-TA","entity_type":"gene"},{"created":"2025-09-29T15:50:23.313851+10:00","panel_name":"Mitochondrial disease","panel_id":203,"panel_version":"0.1035","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: MT-RNR1 were changed from Deafness; Cardiomyopathy to Mitochondrial disease (MONDO:0044970), MT-RNR1-related","entity_name":"MT-RNR1","entity_type":"gene"},{"created":"2025-09-29T15:49:50.602962+10:00","panel_name":"Mitochondrial disease","panel_id":203,"panel_version":"0.1034","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: MT-RNR1 were set to 20301595","entity_name":"MT-RNR1","entity_type":"gene"},{"created":"2025-09-29T15:49:08.310857+10:00","panel_name":"Mitochondrial disease","panel_id":203,"panel_version":"0.1033","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: MT-RNR1: Added comment: DEFINITIVE by ClinGen.\r\n\r\nOver 70 affected individuals reported. Two variants, m.1555A>G and m.1494C>T, are recurrent.\r\n\r\nThese variants are predominantly associated with hearing loss. Some individuals with this variants have normal hearing, others have hearing loss following aminoglycoside exposure, and others have hearing loss and no known aminoglycoside exposure. Age of onset of hearing loss ranged from infancy (after aminoglycoside exposure) to adulthood. Hearing loss has been reported to be variable, stable in some individuals and progressive in others.\r\n\r\nAdditional variants in this gene have been reported to be associated with primary mitochondrial disease, however insufficient clinical detail was provided and/or there was a lack of comprehensive analyses excluding other causes, therefore these additional variants were not included in the ClinGen curation (m.827A>G – PMIDs: 16650816, 16782057, 18261986; m.961delTinsC - PMIDs: 7550368, 10326749; m.1027A>G – PMIDs: 23328039, 21205314, 20100600; m.1095T>C – PMIDs: 11313749, 11079536, 15637703).; Changed publications: 7698299, 16380089, 12920080, 24252789, 9490575, 8285309, 9040738, 7689389; Changed phenotypes: Mitochondrial disease (MONDO:0044970), MT-RNR1-related","entity_name":"MT-RNR1","entity_type":"gene"},{"created":"2025-09-29T15:47:08.112616+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3182","user_name":"Sangavi Sivagnanasundram","item_type":"entity","text":"reviewed gene: NDE1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Microcephaly with lissencephaly and/or hydranencephaly, MONDO:0700116; Mode of inheritance: None","entity_name":"NDE1","entity_type":"gene"},{"created":"2025-09-29T15:42:48.892785+10:00","panel_name":"Mitochondrial disease","panel_id":203,"panel_version":"0.1033","user_name":"Sangavi Sivagnanasundram","item_type":"entity","text":"edited their review of gene: NARS2: Changed phenotypes: Leigh syndrome MONDO:0009723, combined oxidative phosphorylation defect type 24 MONDO:0014547","entity_name":"NARS2","entity_type":"gene"},{"created":"2025-09-29T15:41:26.565921+10:00","panel_name":"Mitochondrial disease","panel_id":203,"panel_version":"0.1033","user_name":"Sangavi Sivagnanasundram","item_type":"entity","text":"changed review comment from: Classified as LIMITED by ClinGen on 19/12/2019 however that was based lack of reported cases at the time of curation.; to: Classified as LIMITED by ClinGen on 19/12/2019 however, that is based on the lack of reported cases at the time of curation.","entity_name":"NARS2","entity_type":"gene"},{"created":"2025-09-29T15:41:10.194591+10:00","panel_name":"Mitochondrial disease","panel_id":203,"panel_version":"0.1033","user_name":"Sangavi Sivagnanasundram","item_type":"entity","text":"reviewed gene: NARS2: Rating: ; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005563; Phenotypes: Leigh syndrome MONDO:0009723; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"NARS2","entity_type":"gene"},{"created":"2025-09-29T15:37:28.970610+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3182","user_name":"Sangavi Sivagnanasundram","item_type":"entity","text":"reviewed gene: NARS: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal","entity_name":"NARS","entity_type":"gene"},{"created":"2025-09-29T15:24:20.048061+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3182","user_name":"Sangavi Sivagnanasundram","item_type":"entity","text":"reviewed gene: NALCN: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal","entity_name":"NALCN","entity_type":"gene"},{"created":"2025-09-29T15:19:11.702101+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3182","user_name":"Sangavi Sivagnanasundram","item_type":"entity","text":"reviewed gene: NAGLU: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal","entity_name":"NAGLU","entity_type":"gene"},{"created":"2025-09-29T15:16:53.415236+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3182","user_name":"Sangavi Sivagnanasundram","item_type":"entity","text":"reviewed gene: NAA10: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: NAA10-related syndrome, MONDO:0100124; Mode of inheritance: None","entity_name":"NAA10","entity_type":"gene"},{"created":"2025-09-29T15:14:42.837206+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3182","user_name":"Sangavi Sivagnanasundram","item_type":"entity","text":"reviewed gene: MYRF: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: MYRF-related cardiac-urogenital syndrome MONDO:0032653; Mode of inheritance: None","entity_name":"MYRF","entity_type":"gene"},{"created":"2025-09-29T15:12:58.767311+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3182","user_name":"Sangavi Sivagnanasundram","item_type":"entity","text":"reviewed gene: MYOT: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: myofibrillar myopathy 3, MONDO:0012215; Mode of inheritance: None","entity_name":"MYOT","entity_type":"gene"},{"created":"2025-09-29T15:08:06.417805+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3182","user_name":"Sangavi Sivagnanasundram","item_type":"entity","text":"commented on gene: PIP5K1C","entity_name":"PIP5K1C","entity_type":"gene"},{"created":"2025-09-29T14:51:29.675032+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3182","user_name":"Sangavi Sivagnanasundram","item_type":"entity","text":"reviewed gene: PITRM1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: spinocerebellar ataxia, autosomal recessive 30, MONDO:0030318; Mode of inheritance: None","entity_name":"PITRM1","entity_type":"gene"},{"created":"2025-09-29T13:15:50.040959+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3182","user_name":"Sangavi Sivagnanasundram","item_type":"entity","text":"reviewed gene: PJA1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: X-linked complex neurodevelopmental disorder, PJA1-related, MONDO:0100148; Mode of inheritance: None","entity_name":"PJA1","entity_type":"gene"},{"created":"2025-09-29T12:48:36.524757+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3182","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: MT-RNR1 as ready","entity_name":"MT-RNR1","entity_type":"gene"},{"created":"2025-09-29T12:48:36.517181+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3182","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: mt-rnr1 has been classified as Green List (High Evidence).","entity_name":"MT-RNR1","entity_type":"gene"},{"created":"2025-09-29T12:44:07.621983+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3182","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: MT-RNR1 as Green List (high evidence)","entity_name":"MT-RNR1","entity_type":"gene"},{"created":"2025-09-29T12:44:07.615154+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3182","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: mt-rnr1 has been classified as Green List (High Evidence).","entity_name":"MT-RNR1","entity_type":"gene"},{"created":"2025-09-29T12:43:53.316522+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3181","user_name":"Zornitza Stark","item_type":"entity","text":"Tag mtDNA tag was added to gene: MT-RNR1.","entity_name":"MT-RNR1","entity_type":"gene"},{"created":"2025-09-29T12:43:40.446668+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3181","user_name":"Zornitza Stark","item_type":"entity","text":"gene: MT-RNR1 was added\ngene: MT-RNR1 was added to Mendeliome. Sources: Expert list\nMode of inheritance for gene gene: MT-RNR1 was set to MITOCHONDRIAL\nPublications for gene: MT-RNR1 were set to 7698299; 16380089; 12920080; 24252789; 9490575; 8285309; 9040738; 7689389\nPhenotypes for gene: MT-RNR1 were set to Mitochondrial disease (MONDO:0044970), MT-RNR1-related\nReview for gene: MT-RNR1 was set to GREEN\nAdded comment: DEFINITIVE by ClinGen.\r\n\r\nOver 70 affected individuals reported. Two variants, m.1555A>G and m.1494C>T, are recurrent.\r\n\r\nThese variants are predominantly associated with hearing loss. Some individuals with this variants have normal hearing, others have hearing loss following aminoglycoside exposure, and others have hearing loss and no known aminoglycoside exposure. Age of onset of hearing loss ranged from infancy (after aminoglycoside exposure) to adulthood. Hearing loss has been reported to be variable, stable in some individuals and progressive in others.\r\n\r\nAdditional variants in this gene have been reported to be associated with primary mitochondrial disease, however insufficient clinical detail was provided and/or there was a lack of comprehensive analyses excluding other causes, therefore these additional variants were not included in the ClinGen curation (m.827A>G – PMIDs: 16650816, 16782057, 18261986; m.961delTinsC - PMIDs: 7550368, 10326749; m.1027A>G – PMIDs: 23328039, 21205314, 20100600; m.1095T>C – PMIDs: 11313749, 11079536, 15637703). \nSources: Expert list","entity_name":"MT-RNR1","entity_type":"gene"},{"created":"2025-09-29T12:24:14.674029+10:00","panel_name":"Mitochondrial disease","panel_id":203,"panel_version":"0.1033","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: MT-ND6 were changed from Mitochondrial cardiomyopathy complex I deficiency; Leber's optic neuropathy; MELAS; Dystonia; Striatal necrosis, bilateral to Mitochondrial disease (MONDO:0044970), MT-ND6-related","entity_name":"MT-ND6","entity_type":"gene"},{"created":"2025-09-29T12:23:45.040783+10:00","panel_name":"Mitochondrial disease","panel_id":203,"panel_version":"0.1032","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: MT-ND6 were set to ","entity_name":"MT-ND6","entity_type":"gene"},{"created":"2025-09-29T12:23:10.488504+10:00","panel_name":"Mitochondrial disease","panel_id":203,"panel_version":"0.1031","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: MT-ND6: Added comment: DEFINITIVE by ClinGen.\r\n\r\nMore than 20 affected individuals reported, the m.14484T>C and m.14487T>C variants are recurrent.\r\n\r\nAffected individuals present with a broad phenotypic spectrum of disease including Leber Hereditary Optic Neuropathy (LHON), mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), and LSS phenotypes, as well as migraines, tremor, multiple sclerosis, and cardiac involvement. The age of onset is also highly variable, ranging from infantile to adult.\r\n\r\nMuscle biopsies revealed isolated complex I deficiency, and complex I and III deficiencies; and complex I deficiency was also seen in fibroblasts and liver. Metabolic screening investigations showed elevated lactate and pyruvate in cerebrospinal fluid (CSF) and blood.\r\n\r\nHeteroplasmy levels in affected individuals ranged from 50% to >95% in skeletal muscle; 25% to >95% in blood, 76% to >95% in fibroblasts, and 65% to >95% in liver; and ranged in healthy family members from undetectable to 92% in blood, undetectable to 95% in urine, 14% to 95% in hair follicles, 16% to 68% in buccal, and was undetectable in muscle in healthy family members.; Changed publications: 5576045, 20019223, 21196529, 10894222, 14684687, 17535832, 19103152, 21749722, 23813926, 25356405, 14595656, 19062322, 11133798, 30741831, 21364701, 2018041; Changed phenotypes: Mitochondrial disease (MONDO:0044970), MT-ND6-related","entity_name":"MT-ND6","entity_type":"gene"},{"created":"2025-09-29T12:22:53.745748+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3180","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: MT-ND6 as ready","entity_name":"MT-ND6","entity_type":"gene"},{"created":"2025-09-29T12:22:53.734797+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3180","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: mt-nd6 has been classified as Green List (High Evidence).","entity_name":"MT-ND6","entity_type":"gene"},{"created":"2025-09-29T12:22:35.014096+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3180","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: MT-ND6 as Green List (high evidence)","entity_name":"MT-ND6","entity_type":"gene"},{"created":"2025-09-29T12:22:34.992361+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3180","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: mt-nd6 has been classified as Green List (High Evidence).","entity_name":"MT-ND6","entity_type":"gene"},{"created":"2025-09-29T12:22:20.350791+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3179","user_name":"Zornitza Stark","item_type":"entity","text":"gene: MT-ND6 was added\ngene: MT-ND6 was added to Mendeliome. Sources: Expert list\nmtDNA tags were added to gene: MT-ND6.\nMode of inheritance for gene gene: MT-ND6 was set to MITOCHONDRIAL\nPublications for gene: MT-ND6 were set to 5576045; 20019223; 21196529; 10894222; 14684687; 17535832; 19103152; 21749722; 23813926; 25356405; 14595656; 19062322; 11133798; 30741831; 21364701; 2018041\nPhenotypes for gene: MT-ND6 were set to Mitochondrial disease (MONDO:0044970), MT-ND6-related\nReview for gene: MT-ND6 was set to GREEN\nAdded comment: DEFINITIVE by ClinGen.\r\n\r\nMore than 20 affected individuals reported, the  m.14484T>C and m.14487T>C variants are recurrent.\r\n\r\nAffected individuals present with a broad phenotypic spectrum of disease including Leber Hereditary Optic Neuropathy (LHON), mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), and LSS phenotypes, as well as migraines, tremor, multiple sclerosis, and cardiac involvement. The age of onset is also highly variable, ranging from infantile to adult.\r\n\r\nMuscle biopsies revealed isolated complex I deficiency, and complex I and III deficiencies; and complex I deficiency was also seen in fibroblasts and liver. Metabolic screening investigations showed elevated lactate and pyruvate in cerebrospinal fluid (CSF) and blood.\r\n\r\nHeteroplasmy levels in affected individuals ranged from 50% to >95% in skeletal muscle; 25% to >95% in blood, 76% to >95% in fibroblasts, and 65% to >95% in liver; and ranged in healthy family members from undetectable to 92% in blood, undetectable to 95% in urine, 14% to 95% in hair follicles, 16% to 68% in buccal, and was undetectable in muscle in healthy family members. \nSources: Expert list","entity_name":"MT-ND6","entity_type":"gene"},{"created":"2025-09-29T12:18:00.137262+10:00","panel_name":"Mitochondrial disease","panel_id":203,"panel_version":"0.1031","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: MT-ND5 were changed from Mitochondrial complex I deficiency; Leber's optic neuropathy; MERFF to Mitochondrial disease (MONDO:0044970), MT-ND5-related","entity_name":"MT-ND5","entity_type":"gene"},{"created":"2025-09-29T12:17:06.487808+10:00","panel_name":"Mitochondrial disease","panel_id":203,"panel_version":"0.1030","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: MT-ND5 were set to ","entity_name":"MT-ND5","entity_type":"gene"},{"created":"2025-09-29T12:16:36.299407+10:00","panel_name":"Mitochondrial disease","panel_id":203,"panel_version":"0.1029","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: MT-ND5: Added comment: DEFINITIVE by ClinGen.\r\n\r\nMore than 20 individuals reported. Two variants are recurrent (m.13513G>A and m.13094T>C).\r\n\r\nAffected individuals present with a broad phenotypic spectrum of disease including Leber Hereditary Optic Neuropathy (LHON); mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS); LSS; myoclonus epilepsy, ragged red fibers (MERRF); and cardiomyopathy. The age of onset is also highly variable, ranging from infantile to adult.\r\n\r\nMuscle biopsies variably revealed ragged red fibers, isolated complex I deficiency, and variable combined deficiencies of complexes I, III, and/or IV. Metabolic screening investigations showed elevated lactate in cerebrospinal fluid (CSF) and blood and urinary excretion of Krebs cycle intermediates.\r\n\r\nHeteroplasmy levels in affected individuals ranged from 28% - 90% in skeletal muscle, 23% to 77% in blood, undetectable to 90% in fibroblasts, 51% - 81% in urine; and ranged in healthy family members from undetectable to 20% in blood, undetectable to 25% to 95% in hair follicles, undetectable to 4-6% muscle, and ranged from 27%-45% in other tissues such as urine and buccal samples in healthy family members.; Changed publications: 17400793, 11938446, 12624137, 18495510, 23918514, 17535832, 29506874, 23034978, 16816025, 9299505, 18977334; Changed phenotypes: Mitochondrial disease (MONDO:0044970), MT-ND5-related","entity_name":"MT-ND5","entity_type":"gene"},{"created":"2025-09-29T12:16:18.363603+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3178","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: MT-ND5 as ready","entity_name":"MT-ND5","entity_type":"gene"},{"created":"2025-09-29T12:16:18.351804+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3178","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: mt-nd5 has been classified as Green List (High Evidence).","entity_name":"MT-ND5","entity_type":"gene"},{"created":"2025-09-29T12:15:43.373703+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3178","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: MT-ND5 as Green List (high evidence)","entity_name":"MT-ND5","entity_type":"gene"},{"created":"2025-09-29T12:15:43.358975+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3178","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: mt-nd5 has been classified as Green List (High Evidence).","entity_name":"MT-ND5","entity_type":"gene"},{"created":"2025-09-29T12:15:23.295145+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3177","user_name":"Zornitza Stark","item_type":"entity","text":"gene: MT-ND5 was added\ngene: MT-ND5 was added to Mendeliome. Sources: Expert list\nmtDNA tags were added to gene: MT-ND5.\nMode of inheritance for gene gene: MT-ND5 was set to MITOCHONDRIAL\nPublications for gene: MT-ND5 were set to 17400793; 11938446; 12624137; 18495510; 23918514; 17535832; 29506874; 23034978; 16816025; 9299505; 18977334\nPhenotypes for gene: MT-ND5 were set to Mitochondrial disease (MONDO:0044970), MT-ND5-related\nReview for gene: MT-ND5 was set to GREEN\nAdded comment: DEFINITIVE by ClinGen.\r\n\r\nMore than 20 individuals reported. Two variants are recurrent (m.13513G>A and m.13094T>C).\r\n\r\nAffected individuals present with a broad phenotypic spectrum of disease including Leber Hereditary Optic Neuropathy (LHON); mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS); LSS; myoclonus epilepsy, ragged red fibers (MERRF); and cardiomyopathy. The age of onset is also highly variable, ranging from infantile to adult.\r\n\r\nMuscle biopsies variably revealed ragged red fibers, isolated complex I deficiency, and variable combined deficiencies of complexes I, III, and/or IV. Metabolic screening investigations showed elevated lactate in cerebrospinal fluid (CSF) and blood and urinary excretion of Krebs cycle intermediates.\r\n\r\nHeteroplasmy levels in affected individuals ranged from 28% - 90% in skeletal muscle, 23% to 77% in blood, undetectable to 90% in fibroblasts, 51% - 81% in urine; and ranged in healthy family members from undetectable to 20% in blood, undetectable to 25% to 95% in hair follicles, undetectable to 4-6% muscle, and ranged from 27%-45% in other tissues such as urine and buccal samples in healthy family members. \nSources: Expert list","entity_name":"MT-ND5","entity_type":"gene"},{"created":"2025-09-29T12:11:18.614287+10:00","panel_name":"Mitochondrial disease","panel_id":203,"panel_version":"0.1029","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: MT-ND4L were changed from Leber's optic atrophy to Mitochondrial disease (MONDO:0044970), MT-ND4L-related","entity_name":"MT-ND4L","entity_type":"gene"},{"created":"2025-09-29T12:10:53.223653+10:00","panel_name":"Mitochondrial disease","panel_id":203,"panel_version":"0.1028","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: MT-ND4L were set to ","entity_name":"MT-ND4L","entity_type":"gene"},{"created":"2025-09-29T12:10:24.179934+10:00","panel_name":"Mitochondrial disease","panel_id":203,"panel_version":"0.1027","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: MT-ND4L as Amber List (moderate evidence)","entity_name":"MT-ND4L","entity_type":"gene"},{"created":"2025-09-29T12:10:24.168808+10:00","panel_name":"Mitochondrial disease","panel_id":203,"panel_version":"0.1027","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: mt-nd4l has been classified as Amber List (Moderate Evidence).","entity_name":"MT-ND4L","entity_type":"gene"},{"created":"2025-09-29T12:09:52.532339+10:00","panel_name":"Mitochondrial disease","panel_id":203,"panel_version":"0.1026","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: MT-ND4L: Added comment: LIMITED by ClinGen.\r\n\r\nSeven 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.; Changed rating: AMBER; Changed publications: 8680405, 11935318, 17003408, 22879922, 24568867; Changed phenotypes: Mitochondrial disease (MONDO:0044970), MT-ND4L-related","entity_name":"MT-ND4L","entity_type":"gene"},{"created":"2025-09-29T12:09:35.962687+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3176","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: MT-ND4L as ready","entity_name":"MT-ND4L","entity_type":"gene"},{"created":"2025-09-29T12:09:35.947542+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3176","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: mt-nd4l has been classified as Amber List (Moderate Evidence).","entity_name":"MT-ND4L","entity_type":"gene"}]}