Published Nov 06, 2026 | 6:00 PM ⚊ Updated Nov 06, 2026 | 6:00 PM
The study analysed 160 patients with HCM and compared their genetic data with 178 ethnically matched healthy controls.
Synopsis: A Hyderabad-led study has identified two previously unreported MYH7 gene variants associated with hypertrophic cardiomyopathy in Indian patients. Found in two families, the variants were classified as likely pathogenic. Researchers say the findings could strengthen genetic screening and early monitoring of relatives at risk of developing the potentially life-threatening heart condition.
Researchers from Hyderabad have identified two previously unreported genetic variants associated with hypertrophic cardiomyopathy (HCM), an inherited condition in which the heart muscle becomes abnormally thick and which can lead to heart failure, abnormal heart rhythms and sudden cardiac death.
The study analysed 160 patients with HCM and compared their genetic data with 178 ethnically matched healthy controls. Researchers from the CSIR-Centre for Cellular and Molecular Biology (CCMB), Osmania University and AIG Hospitals examined the MYH7 gene, which produces a protein essential for heart muscle contraction. The study was published in the November issue of the Journal of the American College of Cardiology: Asia.
They identified 34 variations in the gene, including two novel variants, p.Met684Arg and p.Leu725Pro. Both were located in highly conserved and functionally important regions of the myosin protein, suggesting that they could affect its normal functioning.
The researchers classified both variants as likely pathogenic, based on clinical findings, family inheritance patterns, computational predictions and structural modelling.
“Two novel variants, p.Met684Arg and p.Leu725Pro were absent from gnomAD, 1000 Genomes, ESP, ExAC, and the healthy control cohort supporting their rarity,” the authors said.
“Furthermore, both were located within highly conserved and functionally important regions of the myosin motor domain, suggesting potential functional significance.”
The p.Met684Arg variant was identified in a 52-year-old woman with symptomatic HCM and severe thickening of the heart muscle. Her 26-year-old son, who carried the same variant, had mild thickening.
The second variant, p.Leu725Pro, was found in a 58-year-old man with obstructive HCM and a family history of sudden cardiac death. His 24-year-old daughter also carried the variant and had mild HCM.
The researchers said the differences in disease severity between parents and children suggested that the condition could manifest differently with age, even among members of the same family carrying the same genetic variant.
The p.Met684Arg variant lies in the upper 50-kDa motor domain of the myosin protein, which contributes to actin binding and is connected to the process that generates force during muscle contraction.
The p.Leu725Pro variant is located in the converter domain, a region involved in translating chemical energy into the mechanical movement required for muscle contraction.
Structural modelling indicated that both variants altered molecular interactions, although the overall structure of the protein remained intact.
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Senior Scientist at CCMB Dr Kumarasamy Thangaraj said genetic mutations could be present from birth without producing visible symptoms. The condition may become apparent later as changes develop in the heart muscle.
Identifying disease-associated mutations before structural changes emerge could help doctors recognise people at risk and initiate monitoring and treatment earlier, he said.
Family members, particularly children who carry the same mutation, should undergo monitoring even if they do not have significant symptoms, he added.
The findings also have implications for genetic counselling and screening relatives of people diagnosed with HCM.
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The researchers said the two variants were classified as likely pathogenic based on multiple lines of evidence, including their absence from population databases, inheritance in affected family members, computational predictions and structural modelling.
However, the study did not conduct functional experiments to establish how the variants affect the myosin protein. The family-based evidence was also limited to two affected parent-child pairs.
The researchers reported that the novel variants were found in one of the 160 patients and none of the 178 controls. This difference was not statistically significant, and the authors said the small sample size and rarity of the variants limited statistical power.
They said the findings expand the known range of MYH7 variants among Indian patients with HCM and add genetic data from a population that remains underrepresented in research.
(Edited by Dese Gowda)
