ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.64972+1G>T

dbSNP: rs1057518009
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000414745 SCV000491359 likely pathogenic not provided 2015-12-18 criteria provided, single submitter clinical testing The c.60049+1G>T variant in the TTN gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.60049+1G>T variant was not observed inapproximately 6000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This splice sitevariant destroys the canonical splice donor site in intron 310. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. This variant is located in the A-band region of titin, where the majority of pathogenic truncating variants associated with dilated cardiomyopathy have been reported. Variants associated with tibial muscular dystrophy have also been reported in this region. However, truncating TTN variants have been reported in approximately 3% of control alleles (Herman D et al., 2012). Therefore, we interpret c.60049+1G>T as a likely pathogenic variant.

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