ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.92284A>T (p.Lys30762Ter)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV004018059 SCV004847604 likely pathogenic Primary dilated cardiomyopathy 2019-01-25 criteria provided, single submitter clinical testing The p.Lys28194X variant in TTN has not been reported in individuals with TTN-associated diseases, such as dilated cardiomyopathy and neuromuscular conditions and was absent from large population studies. This nonsense variant leads to a premature termination codon at position 28194, which is predicted to lead to a truncated or absent protein. TTN truncating variants located in exons that are highly expressed in the heart are strongly associated with autosomal dominant DCM, particularly if they are located in the A-band (Herman 2012, Pugh 2014, Roberts 2015). In addition, TTN variants have also been associated with myopathies and other neuromuscular conditions, which usually have autosomal recessive inheritance (Savarese 2016). The p.Lys28194X variant is located in the A-band. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for TTN-associated diseases. ACMG/AMP Criteria applied: PVS1, PM2.

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