ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.86379_86382del (p.Asp28794fs)

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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 RCV004018266 SCV004847295 likely pathogenic Primary dilated cardiomyopathy 2023-07-21 criteria provided, single submitter clinical testing The p.Asp26226SerfsX16 variant in TTN has not been reported in individuals with cardiomyopathy nor in large population studies (gnomAD v.3.1.2). This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 26226 and leads to a premature termination codon 16 amino acids downstream. TTN truncating variants encoded in constitutive exons (PSI >95%) have been found to be significantly associated with dilated cardiomyopathy, regardless of their position in Titin (Roberts 2015 PMID:25589632, Schafer 2017 PMID:27869827). This variant is located in such a highly expressed exon 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 autosomal dominant cardiomyopathy. ACMG/AMP Criteria applied: PVS1, PM2_Supporting.

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