OMIA:002304-9685 : Cardiomyopathy, hypertrophic, TNNT2-related in Felis catus
Categories: Cardiovascular system phene
Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 191045 (gene) , 601494 (trait) , 612422 (trait) , 115195 (trait)
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: Probably autosomal recessive
Considered a defect: yes
Key variant known: no
Key variant is published: no
History: McNamara et al. (2020) report the association between a predicted splice mutation affecting the TNNT2 gene and hypertrophic cardiomyopathy in a single affected Main Coon cat that "was born from consanguineous breeding". Mutations in the TNNT2 gene are associated with 'Cardiomyopathy, dilated' in turkeys (OMIA 000162-9103) and various inherited human cardiomyopathies.
Molecular basis: McNamara et al. (2020) “identified a novel, homozygous intronic variant in cardiac troponin T (TNNT2)” in a “Maine Coon [cat] with cardiomyopathy that tested negative for the MYBPC3 A31P variant” [OMIA000515-9685]. “In silico analysis of the variant suggested that it may affect normal splicing of exon 3 of TNNT2. Both parents tested heterozygous for the mutation, but were unaffected by the disease.”
Schipper et al. (2022) provided convincing evidence against the TNNT2 variant being actually causal: "Based on 160 Maine Coon samples collected in Belgium, Italy, Sweden and the USA, the variant’s allele frequency was estimated to be 0.32. Analysis of the 99 Lives feline whole genome sequencing database showed that the TNNT2 variant also occurs in other breeds, as well as mixed-breed cats. Comparison of 31 affected and 58 healthy cats did not reveal significantly increased odds for HCM in homozygotes. Based on the combined evidence and in agreement with the standards and guidelines for the interpretation of sequence variants, this variant is currently classified as a variant of unknown significance and should not be used for breeding decisions regarding HCM." Because HCM due to mutations in TNNT2 has been reported in humans, the OMIA curators have decided to retain the phene name.
Clinical features: McNamara et al. (2020): “The proband was a privately-owned male pure-bred Maine Coon. At 8 months of age, he presented with left ventricular, right atrial, and borderline left atrial dilatation and borderline septal hypertrophy, with preserved-to-elevated systolic function …, when compared to reference echocardiography values for the Maine Coon (Drourr et al., 2005). Diastolic function could not be quantified as a result of fusion of E and A waves. Progressive enlargement of all four chambers of the heart was noted at 14 months of age, while borderline septal hypertrophy and preserved systolic function was still noted. This was diagnosed as a primary unclassified cardiomyopathy with possible early congestive heart failure.”
Breed: Maine Coon (Cat) (VBO_0100154).
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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.
Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.
|OMIA Variant ID||Breed(s)||Variant Phenotype||Gene||Allele||Type of Variant||Source of Genetic Variant||Reference Sequence||Chr.||g. or m.||c. or n.||p.||Verbal Description||EVA ID||Inferred EVA rsID||Year Published||PubMed ID(s)||Acknowledgements|
|1279||Maine Coon (Cat)||Unknown significance||TNNT2||splicing||Naturally occurring variant||Felis_catus_9.0||F1||g.42204052C>T||c.95-108G>A||This particular variant was a single base pair substitution (G to A) within intron 3, corresponding to c.95-108G > A of ENSFCAG00000004613 (McNamara et al., 2020). Based on the evidence provided by Schipper et al. (2022), this variant is now classified as having "unknown significance". For archival reasons, the variant remains in the OMIA variant table, but its "unknown significance" classification clearly indicates that, on the basis of current knowledge (2 June 2022), it "should not be used for breeding decisions regarding HCM" (Schipper et al., 2022)||2020||33304277|
Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
|2022||Schipper, T., Ohlsson, Å., Longeri, M., Hayward, J.J., Mouttham, L., Ferrari, P., Smets, P., Ljungvall, I., Häggström, J., Stern, J.A., Lyons, L.A., Peelman, L.J., Broeckx, B.J.G. :|
|The TNNT2:c.95-108G>A variant is common in Maine Coons and shows no association with hypertrophic cardiomyopathy. Anim Genet :, 2022. Pubmed reference: 35634705 . DOI: 10.1111/age.13223.|
|2021||Kittleson, M.D., Côté, E. :|
|The feline cardiomyopathies: 1. General concepts. J Feline Med Surg 23:1009-1027, 2021. Pubmed reference: 34693806 . DOI: 10.1177/1098612X211021819.|
|2020||McNamara, J.W., Schuckman, M., Becker, R.C., Sadayappan, S. :|
|A novel homozygous intronic variant in TNNT2 associates with feline cardiomyopathy. Front Physiol 11:608473, 2020. Pubmed reference: 33304277 . DOI: 10.3389/fphys.2020.608473.|
|2005||Drourr, L., Lefbom, B.K., Rosenthal, S.L., Tyrrell, W.D. :|
|Measurement of M-mode echocardiographic parameters in healthy adult Maine Coon cats. J Am Vet Med Assoc 226:734-7, 2005. Pubmed reference: 15776945 . DOI: 10.2460/javma.2005.226.734.|
- Changed by Imke Tammen2 on 18 Dec 2020
- Created by Imke Tammen2 on 18 Dec 2020
- Changed by Frank Nicholas on 02 Jun 2022