ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.83843del (p.Arg27948fs)

dbSNP: rs1703956616
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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 RCV001195430 SCV001365785 likely pathogenic Primary dilated cardiomyopathy 2019-11-13 criteria provided, single submitter clinical testing The p.Arg25380AsnfsX7 variant in TTN has not been previously reported in individuals with dilated cardiomyopathy and was absent from large population studies. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 25380 and leads to a premature termination codon 7 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Frameshift and other truncating variants in TTN are strongly associated with DCM if they impact the exons encoding for the A-band (Herman 2012, Pugh 2014) and/or are located in an exon that is highly expressed in the heart (Roberts 2015). The p.Arg25380AsnfsX7 variant is located in A-band in a highly expressed exon. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for dilated cardiomyopathy. ACMG/AMP Criteria applied: PVS1, PM2.

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