ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.82208C>G (p.Ser27403Ter)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001285590 SCV001472050 likely pathogenic none provided 2020-08-07 criteria provided, single submitter clinical testing The TTN c.82208C>G; p.Ser27403Ter variant, to our knowledge, is not reported in the medical literature or gene-specific databases. This variant is also absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. This variant induces an early termination codon in exon 327 and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Exon 327 is spliced into 100% of TTN transcripts and encodes a segment of the A-band, a critical region of the TTN protein that interacts with myosin and which is disproportionately enriched with truncating variants in individuals affected with dilated cardiomyopathy (Roberts 2015, Schafer 2017). Based on available information, the p.Ser27403Ter variant is considered to be likely pathogenic. References: Linke WA and Hamdani N. Gigantic business: titin properties and function through thick and thin. Circ Res 2014; 114(6): 1052-1068. Roberts AM et al. Integrated allelic, transcriptional, and phenomic dissection of the cardiac effects of titin truncations in health and disease. Sci Transl Med. 2015; 7(270): 270ra6. Schafer S et al. Titin-truncating variants affect heart function in disease cohorts and the general population. Nat Genet. 2017;49(1):46-53.

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