Monogenic hearing loss
Gene: MT-TL1

MT-TL1 (mitochondrially encoded tRNA leucine 1 (UUA/G))
EnsemblGeneIds (GRCh38): ENSG00000209082
EnsemblGeneIds (GRCh37): ENSG00000209082
OMIM: 590050, Gene2Phenotype
MT-TL1 is in 22 panels

4 reviews

Ida Ertmanska (Genomics England Curator)

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, R64 MELAS or MIDD ). 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

Created: 12 Dec 2025, 10:28 a.m.
Last Modified: 12 Dec 2025, 10:28 a.m.
Panel version: 5.49

Achchuthan Shanmugasundram (Genomics England Curator)

Green List (high evidence)

Comment on list classification: As reviewed by Katherine Schon, there is sufficient evidence available for the association of m.3243A>G variant with sensorineural hearing loss. Hence, this gene can be promoted to green rating in the next GMS update.
Created: 24 Jun 2025, 5:45 p.m. | Last Modified: 24 Jun 2025, 5:45 p.m.

Panel Version: 5.15

As per https://www.mitophen.org, there are over 100 different patients reported in peer-reviewed scientific literature with m.3243A>G variant and with sensorineural hearing impairment as one of the presenting phenotypes.

PMID:22403016 - This study clinically evaluated probands and maternal relatives from 34 Dutch families carrying the m.3243A > G variant and showed correlation between the level of heteroplasmy in different samples and the clinical severity of the disease. The variants was identified in 71 adult carriers from these families. Fourty-eight carriers (67.6%) had hearing difficulties - 24 carriers experienced mild deafness, whereas another 19 carriers had moderate deafness (not fully corrected with hearing aid), three carriers had severe deafness (poor even with hearing aid) and two carriers had end stage deafness requiring a cochlear implant.

PMID:23355809 - This study defined the phenotypic spectrum associated with the m.3243A>G variant in 129 patients from 83 unrelated families from the Mitochondrial Disease Patient Cohort Study UK. Of these, 10% of patients exhibited a classical MELAS phenotype, 30% had MIDD, 6% MELAS/MIDD, 5% MIDD/CPEO overlap syndromes, and 3% had Isolated sensorineural hearing loss.

PMID:35455034 - This study conducted a long-term hearing evaluation in 15 patients with MELAS or MIDD who harboured the m.3243A>G variant. The patients had a gradual progression of hearing loss in the early stages and rapid decline in hearing to be profoundly deaf in approximately half of the patients.
Created: 24 Jun 2025, 5:42 p.m. | Last Modified: 24 Jun 2025, 5:42 p.m.

Panel Version: 5.10

Mode of inheritance
MITOCHONDRIAL

Phenotypes
MELAS syndrome caused by mutation in MTTL1, MONDO:0800032; maternally-inherited diabetes and deafness, MONDO:0010785; Sensorineural hearing impairment, HP:0000407

Publications

Created: 24 Jun 2025, 5:42 p.m.
Last Modified: 24 Jun 2025, 5:42 p.m.
Panel version: 5.10

Katherine Schon (University of Cambridge)

Green List (high evidence)

Sensorineural hearing loss is a very common phenotype associated with the m.3243A>G pathogenic variant, as in maternally inherited diabetes and deafness.
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

Mode of pathogenicity
Other

Created: 24 Jun 2025, 10:34 a.m.
Last Modified: 24 Jun 2025, 10:34 a.m.
Panel version: 5.10

Jun Shen (Harvard Medical School)

Red List (low evidence)

MT-TL1 is not associated with a phenotype entry in OMIM.
Created: 9 Feb 2016, 10:07 a.m.

Publications

Created: 7 Feb 2016, 8:59 a.m.

Panel version: 0.105

Details

Mode of Inheritance

MITOCHONDRIAL

Sources

Expert Review Amber
UKGTN

Phenotypes

MELAS syndrome caused by mutation in MTTL1, MONDO:0800032
maternally-inherited diabetes and deafness, MONDO:0010785
Sensorineural hearing impairment, HP:0000407

Tags

locus-type-rna-transfer technical-limitations

OMIM

590050

Clinvar variants

Variants in MT-TL1

Penetrance

Complete

Publications

Panels with this gene

History Filter Activity

12 Dec 2025, Gel status: 2

Added Tag

Ida Ertmanska (Genomics England Curator)

Tag technical-limitations tag was added to gene: MT-TL1.

12 Dec 2025, Gel status: 2

Removed Tag, Removed Tag, Removed Tag

Ida Ertmanska (Genomics England Curator)

Tag Q2_25_ promote_green was removed from gene: MT-TL1. Tag Q2_25_expert_review was removed from gene: MT-TL1. Tag Q2_25_ NHS_review was removed from gene: MT-TL1.

24 Jun 2025, Gel status: 2