Paediatric or syndromic cardiomyopathy

Gene: MYL2

Green List (high evidence)

Comment on mode of inheritance: There are at least 5 unrelated families with biallelic MYL2 variants, and a fatal infantile-onset myocardial disease. The cardiomyopathy presentation was mixed, mostly dilated but also including features of hypertrophic, restrictive, and non-compation cardiomyopathy. Based on available evidence, the mode of inheritance should be updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal.

Created: 25 Feb 2026, 11:29 a.m. | Last Modified: 25 Feb 2026, 11:29 a.m.

Panel Version: 7.93

BIALLELIC CASES:
PMID: 33731536 Tamamitsu et al., 2021
Japanese girl, presented with infantile-onset skeletal myopathy and non-compaction cardiomyopathy at 4 months. She was compound het for MYL2 variants: c.431_432del, p.P144Rfs*57 and c.499T>C, p.*167Qext*?. Proband died at 12 months, elder sister similarly affected with same variants, deceased at 8 months.

PMID: 32453731 Manivannan et al., 2020
Patient with severe infantile onset HCM and mitral valve dysplasia, leading to death before 1 year of age. Proband was homozygous for a frameshift MYL2 variant: c.431_432delCT: p.Pro144Argfs*57;MYL2-fs - consanguineous parents were heterozygous & unaffected. History of multiple infant deaths in the family due to early-onset cardiac disease.

PMID: 31127036 Marttila et al., 2019
Patient with congenital fiber-type disproportion (CFTD) and fatal infantile cardiomyopathy. Individual was homozygous for MYL2 c.188del, p.(Asn63Metfs*7), and heterozygous for NEB:c.25435C>T, p.(Gln8479*) - inherited from his father. MYL2 variant was ultimately thought to explain the phenotype in full.

PMID: 23365102 Weterman et al., 2013
1. Group of 11 individuals from 8 Dutch families with cardioskeletal myopathy with onset and death in infancy, morphological features of muscle type I hypotrophy with myofibrillar disorganization and dilated cardiomyopathy. All affected individuals homozygous for MYL2 splice variant c.403-1G>C, heterozygous carriers unaffected. Founder variant suspected.
2. Two Italian siblings with compound heterozygous mutations, c.431delC, p.(Pro144LeufsX2) and c.432delT, p.(Asp145ThrfsX2) - both had infantile cardiomyopathy.
All individuals died within 6 months after birth. The cardiomyopathy was mixed, mostly dilated but also including features of hypertrophic, restrictive, and non-compation cardiomyopathy.

MYL2 is associated with AD Cardiomyopathy, hypertrophic, 10, MIM:608758 & AR Myopathy, myofibrillar, 12, infantile-onset, with cardiomyopathy, MIM:619424 (OMIM accessed 25th Feb 2026).

Created: 25 Feb 2026, 11:28 a.m. | Last Modified: 25 Feb 2026, 11:28 a.m.

Panel Version: 7.93

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Myopathy, myofibrillar, 12, infantile-onset, with cardiomyopathy, OMIM:619424; Cardiomyopathy, hypertrophic, 10, OMIM:608758

Publications

• 23365102
• 31127036
• 32453731
• 33731536

Green List (high evidence)

Submitted on behalf of the GMS Cardiology specialist group. The group has agreed that this gene should be Green on this panel.

Created: 2 Dec 2019, 3:58 p.m. | Last Modified: 2 Dec 2019, 3:58 p.m.

Panel Version: 0.16

Green List (high evidence)

Cardiomyopathy, hypertrophic, 10 OMIM#608758

Created: 25 Mar 2019, 4:30 p.m.

48 DM variants listed on HGMD -including in Walsh 2017. Also Alfares (2015) Genet Med 17: 880 PubMed: 25611685. Mainly HCM + others. Kabaeva Eur J Hum Genet. 2002 Nov;10(11):741-8: variant associated with paediatric onset HCM but also associated with adult onset disease.

Created: 25 Mar 2019, 4:27 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Variants in this GENE are reported as part of current diagnostic practice