Congenital myopathy

Gene: MT-TN

Red List (low evidence)

After NHS Genomic Medicine Service consideration, the rating of this gene has been updated to red. GLH review concluded that mitochondrial myopathies are not good fit for this panel. R300 Possible mitochondrial disorder - whole mitochondrial genome sequencing would be the more appropriate test.

Created: 11 Dec 2025, 5:32 p.m. | Last Modified: 11 Dec 2025, 5:32 p.m.

Panel Version: 6.43

Comment on list classification: As reviewed by Katherine Schon, pathogenic variants in MT-TN have been reported to cause mitochondrial myopathy. However, there is no clear evidence to suggest that the reported patients had onset of myopathy during infancy/ early childhood. Hence, expert review is sought on whether this gene can be promoted to green rating in the next GMS update.

Created: 27 Jun 2025, 5:20 p.m. | Last Modified: 27 Jun 2025, 5:20 p.m.

Panel Version: 6.22

PMID:8254046 - Two patients were reported with identification of pathogenic variants in two different mitochondrial tRNA genes. One of them had m.5703G>A variant in MT-TN gene and it was associated with isolated ophthalmoplegia. Electromyography tests taken at 27 years of age were compatible with myopathy. However, the actual age of onset of myopathy was not reported.

PMID:16908752 - A 13-year-old male patient with multi organ failure was identified with m.5728C>T variant in MT-TN gene. The patient had initial symptoms since 2 years of age and muscle weakness was first reported at 10 years.

PMID:23696415 - This study identified nine different mt-tRNA variants in nine families, of which one was m.5690A>G variant from MT-TN gene. The patient had the onset of disease at 13 years and presented with chronic progressive external ophthalmoplegia (CPEO), ptosis and proximal myopathy.

PMID:31026515 - A nine-year old female was identified with m.5728C>T variant and has a milder clinical phenotype with isolated ptosis and ophthalmoplegia. She was reported to have the onset of ptosis at around 8 years of age.

Created: 27 Jun 2025, 5:16 p.m. | Last Modified: 27 Jun 2025, 5:16 p.m.

Panel Version: 6.19

Mode of inheritance
MITOCHONDRIAL

Phenotypes
inborn mitochondrial myopathy, MONDO:0009637

Publications

• 8254046
• 16908752
• 23696415
• 31026515

Green List (high evidence)

m.5690A>G, m.5703G>A and m.5728T>C pathogenic variantas in MT-TN have been reported to cause myopathy.

Created: 24 Jun 2025, 10:53 a.m. | Last Modified: 24 Jun 2025, 10:53 a.m.

Panel Version: 6.10

Mode of inheritance
MITOCHONDRIAL

Publications

• 23696415
• 31026515
• 8254046

Mode of pathogenicity
Other