Monogenic hearing loss

Gene: MT-TK

After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains Amber. The GMS reviewers commented as follows: More appropriate for specialist mitochondrial lab to test for this - 1) Alternative panel test available for this gene (R300 - Possible mitochondrial disorder - whole mitochondrial genome sequencing). 2) May not be technically feasible for all laboratories to include this gene on the panel.

Created: 12 Dec 2025, 10:28 a.m. | Last Modified: 12 Dec 2025, 10:28 a.m.

Panel Version: 5.49

Green List (high evidence)

Comment on list classification: As reviewed by Katherine Schon, there is sufficient evidence available for the association of variants in MT-TK gene with sensorineural hearing loss. Hence, this gene can be promoted to green rating in the next GMS update.

Created: 26 Jun 2025, 9:11 p.m. | Last Modified: 26 Jun 2025, 9:11 p.m.

Panel Version: 5.18

As per MitoPhen database (https://www.mitophen.org) there are >10 patients reported with m.8363G>A variant in MT-TK gene and with sensorineural hearing impairment as one of the phenotypes. There are >20 patients reported in MitoPhen with m.8344A>G variant and with sensorineural hearing impairment as one of the phenotypes.

PMID:8651277 - Two unrelated families were reported with a syndrome consisting of encephalomyopathy, sensorineural hearing loss, and hypertrophic cardiomyopathy. They were identified with the m.8363G>A variant.

PMID:1899320 - The m.8344A>G variant was detected in five of seven Italian families reported in this study with MERRF. Hearing loss was reported as a clinical presentation in patients from four of these families.

PMID:23224446 - 12 unrelated patients were reported with mitochondrial disorders in whom psychiatric symptoms were a prominent aspect of the clinical presentation. Of these, one patient was identified with m.8363G>A variant, who had bilateral hearing loss as one of the clinical presentations.

Created: 26 Jun 2025, 9:07 p.m. | Last Modified: 26 Jun 2025, 9:07 p.m.

Panel Version: 5.15

Mode of inheritance
MITOCHONDRIAL

Phenotypes
MERRF syndrome, MONDO:0010790; Sensorineural hearing impairment, HP:0000407

Publications

• 8651277
• 1899320
• 23224446

Green List (high evidence)

SNHL has been reported with the m.8363G>A variant in MT-TK and with the m.8344A>G variant as part of MERRF (myoclonic epilepsy, ragged red fibres).

Created: 24 Jun 2025, 10:34 a.m. | Last Modified: 24 Jun 2025, 10:34 a.m.

Panel Version: 5.10

Mode of inheritance
MITOCHONDRIAL

Publications

• https://www.ncbi.nlm.nih.gov/books/NBK1520/ (further reference from Table 2)
• 8651277

Mode of pathogenicity
Other