2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Unraveling the Phenotypic Consequences of Variation in the <em>TTN</em> Gene

Pdf Summary

The TTN gene encodes a protein called titin that is important for proper heart muscle function. While most mutations in this gene have no effect on the heart, certain mutations have been associated with cardiomyopathies. To better understand the relationship between specific mutations in the TTN gene and the development of cardiomyopathy, researchers examined TTN variants in a population study called HerediGene. They analyzed data from 473 individuals with predicted loss of function variants in the TTN gene and looked at their medical records, demographic information, and variant characteristics.<br /><br />They found that a significant percentage of individuals with predicted loss of function variants in the TTN gene had a diagnosis of cardiomyopathy, even though most of these variants were not present in a database called ClinVar. They also observed that males were more likely to have a cardiomyopathy diagnosis than females, even after adjusting for the specific location of the variant in the TTN gene. The researchers noted that this finding suggests that there may be a protective effect of sex on the development of cardiomyopathy.<br /><br />In terms of the specific location of the variants within the TTN gene, variants in the A-band region were most strongly associated with cardiomyopathy and were also associated with earlier onset of the condition. Variants in other regions of the gene, such as the I-band, M-band, and Z-disk, were less likely to be associated with cardiomyopathy.<br /><br />Overall, the study highlights the complexity of understanding TTN gene variants and the need for further functional testing. The findings also emphasize the importance of considering the location and type of TTN variants in assessing the risk of developing cardiomyopathy.

Asset Subtitle

Presenting Author - Nephi Walton, MD, MS, FACMG, FAMIA; Co-Author - Jeffrey L. Anderson, MD; Co-Author - Melanie Emmerson, CGC; Co-Author - Kirk Knowlton, MD; Co-Author - Jared M. Evans, MS; Co-Author - Bryce Christensen, PhD; Co-Author - Stacey Knight, PhD;

Meta Tag

Bioinformatics

Cardiac/circulatory disorders

Cardiovascular System

Genetic Testing

Genome sequencing

Genomic Structure

Genotype-Phenotype Correlations

Natural History

Phenotype

Population Genetics

Risk Assessment

Sequencing

Structure/Function

Co-Author Jeffrey L. Anderson, MD

Co-Author Melanie Emmerson, CGC

Co-Author Kirk Knowlton, MD

Co-Author Jared M. Evans, MS

Co-Author Bryce Christensen, PhD

Co-Author Stacey Knight, PhD

Presenting Author Nephi Walton, MD, MS, FACMG, FAMIA

Keywords

TTN gene

titin protein

heart muscle function

mutations

cardiomyopathies

HerediGene

loss of function variants

sex

A-band region

functional testing