ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.57215del (p.Gly19072fs)

dbSNP: rs397517628
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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 RCV000040389 SCV000064080 likely pathogenic Primary dilated cardiomyopathy 2020-12-21 criteria provided, single submitter clinical testing The p.Gly16504GlufsX12 variant in TTN has been reported in 1 individual with infant onset left ventricular dilation and their reportedly unaffected parent (>50 years; Pugh 2014 PMID: 24503780) and was absent from larger population studies. This variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at codon 16504 and leads to a premature termination 12 codons downstream. This alteration is then predicted to lead to a truncated protein. Frameshift and other truncating variants in TTN are strongly associated with dilated cardiomyopathy (DCM), particularly if they are located in the exons encoding for the A-band (Herman 2012 PMID:22335739, Pugh 2014 PMID:24503780) and/or are located in an exon that is highly expressed in the heart (Roberts 2015 PMID:25589632), which is the case for the p.Gly16504GlufsX12 variant. 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 DCM. ACMG/AMP Criteria applied: PM2_supporting, PVS1.

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