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| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v5.28 | TNNI1 | Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: TNNI1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v5.25 | TNNI1 | Arina Puzriakova Tag Q2_25_ promote_green was removed from gene: TNNI1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v5.24 | TNNI1 | Arina Puzriakova commented on gene: TNNI1: The rating of this gene has been updated to green and the mode of inheritance updated to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal following NHS Genomic Medicine Service approval. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v5.23 | TNNI1 |
Arina Puzriakova Source NHS GMS was added to TNNI1. Source Expert Review Green was added to TNNI1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence) |
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| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v5.7 | TNNI1 | Arina Puzriakova Classified gene: TNNI1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v5.7 | TNNI1 | Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update. 3 families with biallelic LOF variants and 3 families with monoallelic GOF variants, presenting with a hypo- or hypercontractile phenotype, respectively. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v5.7 | TNNI1 | Arina Puzriakova Gene: tnni1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v5.6 | TNNI1 | Arina Puzriakova Mode of inheritance for gene: TNNI1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v5.5 | TNNI1 | Arina Puzriakova Phenotypes for gene: TNNI1 were changed from Hypocontractile (AR LOF) or Hypercontractile (AD GOF) muscle disease to Hypocontractile (AR LOF) or Hypercontractile (AD GOF) muscle disease | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v5.4 | TNNI1 | Arina Puzriakova Phenotypes for gene: TNNI1 were changed from to Hypocontractile (AR LOF) or Hypercontractile (AD GOF) muscle disease | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v5.4 | TNNI1 | Arina Puzriakova Publications for gene: TNNI1 were set to PMID: 38569017 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v5.3 | TNNI1 | Arina Puzriakova Tag Q2_25_ promote_green tag was added to gene: TNNI1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v5.3 | TNNI1 |
Arina Puzriakova changed review comment from: - PMID: 38569017 (2024) - 9 individuals from 3 families with biallelic LOF variants in the TNNI1 gene, manifesting with early-onset myopathy with progressive muscle weakness (proximal more than distal) and rod formation on histology. 2 individuals from different families presented with severe infantile weakness with minimal attainment of motor milestones. 3 individuals from 2 families had mild/moderate contractures. Also another 2 families with heterozygous GOF variants, resulting in hypercontractile disease with a constellation of symptoms including muscle cramping, myalgias, stiffness, and rod formation. 4/5 patients reported normal muscle strength and there is no mention of contractures. Recognition of symptoms ranged from childhood to adulthood. Functional studies in zebrafish demonstrate variant-specific pathomechanisms, manifesting as either a hypo- or a hypercontractile phenotype. - PMID: 34934811 (2021) - Japanese family with 3 affected individuals with proximal arthrogryposis and elevated CK, albeit without muscle weakness. A presumed GOF heterozygous c.523A>T, p.K175* TNNI1 variant was identified (2 genotyped). Muscle biopsy demonstrated a moth-eaten appearance and mild fibre size variation in type 1 fibres, and electron microscopic analysis revealed type 1 fibre Z disk streaming. No functional studies were done.; to: - PMID: 38569017 (2024) - 9 individuals from 3 families with biallelic LOF variants in the TNNI1 gene, manifesting with early-onset myopathy with progressive muscle weakness (proximal more than distal) and rod formation on histology. 2 individuals from different families presented with severe infantile weakness with minimal attainment of motor milestones. 3 individuals from 2 families had mild/moderate contractures. Also another 2 families with heterozygous GOF variants, resulting in hypercontractile disease with a constellation of symptoms including muscle cramping, myalgias, stiffness, and rod formation. 4/5 patients reported normal muscle strength and there is no mention of contractures. Recognition of symptoms ranged from childhood to adulthood. Functional studies in zebrafish demonstrate variant-specific pathomechanisms, manifesting as either a hypo- or a hypercontractile phenotype. - PMID: 34934811 (2021) - Japanese family with 3 affected individuals with proximal arthrogryposis and elevated CK, albeit without muscle weakness. A presumed GOF heterozygous c.523A>T, p.K175* TNNI1 variant was identified (2 genotyped). Muscle biopsy demonstrated a moth-eaten appearance and mild fibre size variation in type 1 fibres, and electron microscopic analysis revealed type 1 fibre Z disk streaming. No functional studies were done. |
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| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v5.3 | TNNI1 | Arina Puzriakova reviewed gene: TNNI1: Rating: GREEN; Mode of pathogenicity: None; Publications: 38569017, 34934811; Phenotypes: Hypocontractile (AR LOF) or Hypercontractile (AD GOF) muscle disease; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.35 | TNNI1 |
Dmitrijs Rots gene: TNNI1 was added gene: TNNI1 was added to Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies. Sources: Literature Mode of inheritance for gene: TNNI1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: TNNI1 were set to PMID: 38569017 Review for gene: TNNI1 was set to GREEN Added comment: The study describes: "We identified recessive loss-of-function TNNI1 variants as well as dominant gain-of-function TNNI1 variants as a cause of muscle disease, each with distinct physiological consequences and disease mechanisms. We identified three families with biallelic TNNI1 variants (F1: p.R14H/c.190-9G>A, F2 and F3: homozygous p.R14C), resulting in loss of function, manifesting with early-onset progressive muscle weakness and rod formation on histology. We also identified two families with a dominantly acting heterozygous TNNI1 variant (F4: p.R174Q and F5: p.K176del), resulting in gain of function, manifesting with muscle cramping, myalgias, and rod formation in F5." Sources: Literature |
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