ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.55161_55164dup (p.Val18389fs)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PreventionGenetics, part of Exact Sciences RCV004724578 SCV005336270 likely pathogenic TTN-related disorder 2024-04-29 no assertion criteria provided clinical testing The TTN c.55161_55164dupTCTG variant is predicted to result in a frameshift and premature protein termination (p.Val18389Serfs*4). To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. This variant is located in the A-band region of the protein in which truncating TTN variants have been found more frequently in dilated cardiomyopathy patients than in controls (Herman et al. 2012. PubMed ID: 22335739). RNAseq studies from heart tissue indicate this exon is commonly included in TTN mRNA transcripts (PSI of 90%-100%); however, this analysis in muscle tissue was not performed (Roberts et al. 2015. PMID: 25589632; https://cardiodb.org/titin/titin_transcripts.php). TTN truncating variants are reported in 1-2% of presumably healthy individuals and occur more frequently in exons with low PSI values, indicating this variant is more likely to be disease causing (Herman et al. 2012. PMID: 22335739; Roberts et al. 2015. PMID: 25589632). In summary, this variant is interpreted as likely pathogenic for both autosomal dominant and autosomal recessive TTN-related disorders.

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