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| Mendeliome v1.3207 | MT-TM |
Zornitza Stark gene: MT-TM was added gene: MT-TM was added to Mendeliome. Sources: Expert list mtDNA tags were added to gene: MT-TM. Mode of inheritance for gene gene: MT-TM was set to MITOCHONDRIAL Publications for gene: MT-TM were set to 9633749; 24711008; 25468263; 30739820; 11335700; 31488384; 31022467; 29174468 Phenotypes for gene: MT-TM were set to mitochondrial disease (MONDO:0044970), MT-TM-related Review for gene: MT-TM was set to GREEN Added comment: DEFINITIVE by ClinGen. Multiple individuals reported. The condition was first described in a 10-year-old girl with exercise intolerance, myopathy, and short stature with mildly elevated serum lactate. Subsequent publications have shown a consistent phenotype involving a mitochondrial myopathy (typically childhood onset) with elevated lactate. Chronic external progressive ophthalmoplegia (CPEO) is not common but has been reported. Basal ganglia lesions and Leigh syndrome spectrum/mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) overlap have also been reported in one patient. Retinitis pigmentosa has also been reported. Muscle biopsy often shows classic findings of mitochondrial myopathy with COX-negative and ragged red (or blue) fibers. Combined OXPHOS deficiencies in muscle are also observed. Sources: Expert list |
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| Mendeliome v1.3205 | MT-TL2 |
Zornitza Stark gene: MT-TL2 was added gene: MT-TL2 was added to Mendeliome. Sources: Expert list mtDNA tags were added to gene: MT-TL2. Mode of inheritance for gene gene: MT-TL2 was set to MITOCHONDRIAL Publications for gene: MT-TL2 were set to 8923013; 12398839; 19718780; 18977334; 21819490; 15649400; 15591266; 23847141; 20022607; 29052516 Phenotypes for gene: MT-TL2 were set to Mitochondrial disease (MONDO:0044970), MT-TL2-related Review for gene: MT-TL2 was set to GREEN Added comment: DEFINITIVE by ClinGen. Multiple individuals reported with a range of clinical phenotypes, including CPEO, retinopathy, hearing loss, myopathy, exercise intolerance, and peripheral neuropathy. There is a substantial amount of functional evidence for the reported variants, including numerous single fiber studies, and respiratory chain analyses showing clear evidence of OXPHOS defects Sources: Expert list |
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| Mendeliome v1.3198 | MT-TI |
Zornitza Stark gene: MT-TI was added gene: MT-TI was added to Mendeliome. Sources: Expert list mtDNA tags were added to gene: MT-TI. Mode of inheritance for gene gene: MT-TI was set to MITOCHONDRIAL Publications for gene: MT-TI were set to 15121771; 21982779; 23395828; 16120360; 9473477; 12767666; 10065021; 7646516; 20884012; 21292040; 1632786; 23696415; 34607911 Phenotypes for gene: MT-TI were set to Mitochondrial disease (MONDO:0044970), MT-TI-related Review for gene: MT-TI was set to GREEN Added comment: DEFINITIVE by ClinGen. More than 10 individuals reported. Clinical presentations included LSS, myoclonic epilepsy with ragged red fibers (MERRF) and chronic progressive external ophthalmoplegia (CPEO), in addition to rhabdomyolysis, cardiomyopathy, encephalopathy, exercise intolerance, muscle weakness, hypertension2, hypercholesterolaemia, and hypomagnesaemia. Heteroplasmy levels of MT-TI can be variable in tissues from the same individual. In general, variants tend to be lower in tissues such as blood, saliva, and buccal swab and urine and muscle heteroplasmy levels tend to be higher. Sources: Expert list |
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| Mendeliome v1.3191 | MT-TF |
Zornitza Stark gene: MT-TF was added gene: MT-TF was added to Mendeliome. Sources: Expert list Mode of inheritance for gene gene: MT-TF was set to MITOCHONDRIAL Publications 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 Phenotypes for gene: MT-TF were set to Mitochondrial disease (MONDO:0044970), MT-TF-relatedn Review for gene: MT-TF was set to GREEN Added comment: DEFINITIVE by ClinGen. Over 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. 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. Laboratory investigations showed variable lactate levels (normal to elevated in blood, cerebrospinal fluid, and/or urine) and elevated creatine kinase (CK). Heteroplasmy 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. Sources: Expert list |
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| Mendeliome v1.3189 | MT-TE |
Zornitza Stark gene: MT-TE was added gene: MT-TE was added to Mendeliome. Sources: Expert list Mode of inheritance for gene gene: MT-TE was set to MITOCHONDRIAL Publications for gene: MT-TE were set to 8155739; 21194154; 17715279; 23334599; 7726155; 7726154; 9353617; 15048886; 15670724; 23847141; 23334599; 17266923; 17056256 Phenotypes for gene: MT-TE were set to Mitochondrial disease (MONDO:0044970), MT-TE-related Review for gene: MT-TE was set to GREEN Added comment: DEFINITIVE by ClinGen. More 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. Heteroplasmy levels in affected individuals were highest in muscle when multiple tissues were assessed, and were variable in other tissues when tested. Sources: Expert list |
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| Mendeliome v1.1224 | CPEB1 | Zornitza Stark Phenotypes for gene: CPEB1 were changed from Primary ovarian insufficiency to Primary ovarian insufficiency, MONDO:0005387, CPEB1-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9949 | CPEB1 | Bryony Thompson Marked gene: CPEB1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9949 | CPEB1 | Bryony Thompson Gene: cpeb1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9949 | CPEB1 | Bryony Thompson Classified gene: CPEB1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9949 | CPEB1 | Bryony Thompson Gene: cpeb1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9948 | CPEB1 |
Bryony Thompson gene: CPEB1 was added gene: CPEB1 was added to Mendeliome. Sources: Literature SV/CNV tags were added to gene: CPEB1. Mode of inheritance for gene: CPEB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CPEB1 were set to 34794894; 33095795; 32354341; 30689869; 11702780 Phenotypes for gene: CPEB1 were set to Primary ovarian insufficiency Review for gene: CPEB1 was set to AMBER Added comment: Large CNVs including CPEB1 mainly reported, but also include BNC1. PMID: 33095795 - 1 POI case with missense variant p.R87C, which has 101 hets in gnomAD v2.1 (too common for a Mendelian dominantly inherited disease). Also another POI case with an 83.8Kb deletion including CPEB1. PMID: 32354341 - 1 primary amenorrhea case heterozygous deletion of exons 8-12 of CPEB1 PMID: 30689869 - 6 POI cases (including previously reported) with a 15q25.2 deletion including CPEB1, but also including POI gene BNC1. Also, a homozygous microdeletion involving CPEB1 intron 1 in one case. PMID: 11702780 - knockout mouse model had vestigial ovaries devoid of oocytes Sources: Literature |
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| Mendeliome v0.9272 | CPE | Zornitza Stark Publications for gene: CPE were set to 26120850; 32936766 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9271 | CPE | Zornitza Stark Classified gene: CPE as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9271 | CPE | Zornitza Stark Gene: cpe has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9270 | CPE | Arina Puzriakova reviewed gene: CPE: Rating: GREEN; Mode of pathogenicity: None; Publications: 34383079; Phenotypes: Intellectual developmental disorder and hypogonadotropic hypogonadism, OMIM:619326; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7631 | CPE | Zornitza Stark Marked gene: CPE as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7631 | CPE | Zornitza Stark Gene: cpe has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7631 | CPE | Zornitza Stark Classified gene: CPE as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7631 | CPE | Zornitza Stark Gene: cpe has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7630 | CPE |
Zornitza Stark gene: CPE was added gene: CPE was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: CPE was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CPE were set to 26120850; 32936766 Phenotypes for gene: CPE were set to Intellectual developmental disorder and hypogonadotropic hypogonadism, MIM# 619326 Review for gene: CPE was set to AMBER Added comment: Four affected individuals from two unrelated families reported, bi-allelic LoF variants. Sources: Expert Review |
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