Congenital myopathy

Gene: MT-TL1

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 the myopathy phenotype has predominantly been reported to be relatively late-onset, expert review is sought from the Genomic Medicine Service on promotion of this gene to green rating on this panel.

Created: 25 Jun 2025, 10:57 a.m. | Last Modified: 25 Jun 2025, 10:57 a.m.

Panel Version: 6.13

As reviewed by Katherine Schon, myopathy is part of the phenotypic spectrum that is caused by m.3243A>G variant from MT-TL1 gene. Mitochondrial myopathy can also occur in isolation as reported in the 24-year-old female patient reported in PMID:33484420.

As reviewed by Helen Brittain below, the majority of the patients developed phenotype later in their life and not in infancy. However, it should be noted there are a small proportion of cases with onset of myopathy during childhood.

Below are three published cases from them:
PMID:8122892 - A Japanese girl reported with muscle weakness at around 6 years 8 months.
PMID:8559168 - A 14-year-old boy was reported with seizures and multifocal head myoclonus from the age of two and had muscle weakness on examination at the age of 10.
PMID:18391161 - One of two patients was reported with MELAS syndrome including myopathy since childhood.

Created: 25 Jun 2025, 10:52 a.m. | Last Modified: 25 Jun 2025, 10:52 a.m.

Panel Version: 6.10

Mode of inheritance
MITOCHONDRIAL

Phenotypes
MELAS syndrome caused by mutation in MTTL1, MONDO:0800032; inborn mitochondrial myopathy, MONDO:0009637

Publications

• 8122892
• 8559168
• 18391161

Green List (high evidence)

Myopathy is a recognised part of the phenotype in m.3243A>G and can occasionally occur in isolation as the presenting symptom. The 3302A>G variant also causes 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

• 23355809
• 20458543
• 33484420

Mode of pathogenicity
Other

Red List (low evidence)

Mode of inheritance
MITOCHONDRIAL

Phenotypes
MITOCHONDRIAL MYOPATHY, ENCEPHALOPATHY, LACTIC ACIDOSIS, AND STROKE-LIKE EPISODES; MELAS 540000

Red List (low evidence)

Comment when marking as ready: Mitochondrial gene. Well established cause of MELAS / MERRF / MIDD but none of these would be expected to present at birth / early infancy with myopathy.

Created: 3 Feb 2017, 12:13 p.m.

Mitochondrial gene. Well established cause of MELAS / MERRF / MIDD but none of these would be expected to present at birth / early infancy with myopathy.

Created: 31 Jan 2017, 10:21 a.m.

Mode of inheritance
MITOCHONDRIAL

Phenotypes
MITOCHONDRIAL MYOPATHY, ENCEPHALOPATHY, LACTIC ACIDOSIS, AND STROKE-LIKE EPISODES; MELAS 540000