Cardiac arrhythmias - additional genes

Gene: TANGO2

Green List (high evidence)

Comment on list classification: There are over 30 unrelated patients reported with biallelic TANGO2 variants and with cardiac arrhythmia as one of the clinical presentations of the TANGO2-related disorder.

Expert review is being sought on the promotion of this gene to green rating on this panel. This is due to this gene being not previously approved for promotion to green rating on this panel by the NHS Genomic Medicine Service.

Created: 5 Sep 2025, 10:25 a.m. | Last Modified: 5 Sep 2025, 1:09 p.m.

Panel Version: 3.6

Comment on phenotypes: This gene has been associated with relevant phenotypes in both OMIM (MIM #616878, accessed on 05 September 2025) and Gene2Phenotype (TANGO2-related infancy-onset recurrent metabolic crises with encephalocardiomyopathy with 'definitive' rating on the DD panel).

Created: 5 Sep 2025, 10:18 a.m. | Last Modified: 5 Sep 2025, 10:18 a.m.

Panel Version: 3.4

PMID:26805781 (2016) reported the identification of biallelic variants (a missense variant and two different intragenic deletions) in 12 patients from nine unrelated families with episodic rhabdomyolysis, hypoglycemia, hyperammonemia, and susceptibility to life-threatening cardiac tachyarrhythmias. Life-threatening cardiac tachyarrhythmia presented as torsade de pointes or ventricular tachycardia in 4 of 12 patients.

PMID:26805782 (2016) reported the identification of three different biallelic truncating variants in TANGO2 genes in three unrelated patients with infantile-onset metabolic disorder characterised by encephalopathy, hypoglycemia, rhabdomyolysis, arrhythmias, and laboratory findings suggestive of a defect in mitochondrial fatty acid oxidation.

PMID:30245509 (2018) reported the identification of biallelic TANGO2 variants (five different variants including the previously described exon 3-9 intragenic deletion in either homozygous or compound heterozygous states) in 14 individuals from 11 unrelated families with a complex clinical phenotype including primarily neurological presentations. Arrhythmia was reported in five of 14 patients.

PMID:31339582 (2020) reported nine patients from seven unrelated families with biallelic TANGO2 variants (exons 3-9 deletion and small variants). All, but one patient showed cardiac arrhythmias.

PMID:32929747 (2021) conducted a retrospective analysis of patients with a diagnosis of TANGO2 disease, where seven single nucleotide variants (five were novel), 2 small deletions and exons 3-9 deletion were identified in 20 patients from 14 families. 12 of these patients had cardiac abnormalities - long QT in ten, Brugada pattern in two, and cardiac arrhythmia in six.

PMID:35568137 (2022) conducted a retrospective multicentre chart review of TANGO2 deficiency disorder patients admitted with cardiac crises, where 27 children were admitted for 43 cardiac crises at 14 centres. Arrhythmias included ventricular tachycardia in 21 (78%), supraventricular tachycardia in 3 (11%), and heart block in 1 (4%). Nineteen patients (70%) developed cardiomyopathy, and 20 (74%) experienced a cardiac arrest.

PMID:40156300 (2025) reported two unrelated patients with biallelic TANGO2 pathogenic variants (homozygous deletion of exons 4-6 in one and c.605+1G>A in the other). Both patients developed ventricular tachyarrhythmias, and the echocardiogram showed cardiomyopathy.

Created: 5 Sep 2025, 10:16 a.m. | Last Modified: 5 Sep 2025, 1:08 p.m.

Panel Version: 3.6

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration, OMIM:616878; recurrent metabolic encephalomyopathic crises-rhabdomyolysis-cardiac arrhythmia-intellectual disability syndrome, MONDO:0018820

Publications

• 26805781
• 26805782
• 30245509
• 31339582
• 32929747
• 35568137
• 40156300

After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed.

Created: 3 Mar 2022, 10:50 a.m. | Last Modified: 3 Mar 2022, 10:50 a.m.

Panel Version: 1.15

Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag).

Created: 20 Oct 2020, 3:09 p.m. | Last Modified: 20 Oct 2020, 3:09 p.m.

Panel Version: 1.11

Green List (high evidence)

Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 10 variants reported in at least 14 unrelated cases, with arrhythmias in 8 unrelated cases.

Gene suggested by Rowenna Roberts, Clinical Scientist.
Sources: Expert Review

Created: 5 May 2020, 11:27 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration 616878

Publications

• 26805782
• 30245509