Hypertrophic cardiomyopathy

Gene: MT-TV

After NHS Genomic Medicine Service consideration, the rating of this gene has been updated to Grey. The GMS reviewers commented as follows: More appropriate for specialist mitochondrial lab to test for this - 1) Lack of evidence that HCM can be the primary/sole presenting feature. Syndromic phenotypes are beyond the scope of this panel. 2) Alternative panel test available for this gene (R300 - Possible mitochondrial disorder - whole mitochondrial genome sequencing). 3) May not be technically feasible for all laboratories to include this gene on this panel

Created: 11 Dec 2025, 4:05 p.m. | Last Modified: 11 Dec 2025, 4:05 p.m.

Panel Version: 5.22

I don't know

Comment on list classification: There are at least three unrelated cases reported with MT-TV variants and with hypertrophic cardiomyopathy. However, HCM is part of a syndromic phenotype.

R131 is only intended for genes associated with isolated HCM and not for syndromic genes. Hence, expert review is sought on whether this gene can be promoted to green rating on this panel.

This gene is therefore better placed as a green rated gene on the WGS clinical indication R135 Paediatric or syndromic cardiomyopathy.

Created: 27 Jun 2025, 10:38 a.m. | Last Modified: 27 Jun 2025, 10:38 a.m.

Panel Version: 5.12

PMID:15320572 - The m.1644G>A variant in MT-TV gene has been reported in a patient with severe hypertrophic cardiomyopathy associated with MELAS. The familial phenotype included hypertrophic cardiomyopathy and MELAS, clinically mild cardiac hypertrophy, and deafness.

PMID:21986556 - Two patients were identified with variants in MT-TV gene (one with m.1628C>T variant and the other with m.1644G>A variant) by a systematic search in a series of patients suspected of mitochondrial cardiomyopathy. The patient with m.1628C>T variant had mild hypertrophic cardiomyopathy as one of the clinical presentations, while the other patient had pronounced cardiomegaly and biventricular hypertrophy.

PMID:34298071 - This study reported 223 paediatric mitochondria disease patients with confirmed genetic diagnosis, of which one patient had m.1644G>A variant. The patient had hypertrophic cardiomyopathy.

Created: 27 Jun 2025, 10:34 a.m. | Last Modified: 27 Jun 2025, 10:34 a.m.

Panel Version: 5.9

Mode of inheritance
MITOCHONDRIAL

Phenotypes
MELAS syndrome, MONDO:0010789; hypertrophic cardiomyopathy, MONDO:0005045

Publications

• 15320572
• 21986556
• 34298071

Green List (high evidence)

The m.1644G>A pathogenic variant has been associated with hypertrophic cardiomyopathy and c.1612C>T was also observed in an individual with hypertrophic cardiomyopathy (https://www.heartlungcirc.org/article/S1443-9506(22)00155-X/)

Created: 24 Jun 2025, 10:19 a.m. | Last Modified: 24 Jun 2025, 10:19 a.m.

Panel Version: 5.3

Mode of inheritance
MITOCHONDRIAL

Publications

• 34298071
• 15320572

Mode of pathogenicity
Other