ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.475_476insG (p.Tyr159Ter)

dbSNP: rs794729377
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000184382 SCV000237007 uncertain significance not provided 2014-03-25 criteria provided, single submitter clinical testing c.475_476insG: p.Tyr159Stop (Y159X) in exon 4 of the TTN gene (NM_001256850.1). The normal sequence with the base that is inserted in braces is: CTCT{G}ACAG. The c.475_476insG variant in the TTN gene has not been reported to our knowledge. This variant was not observed in approximately 6,500 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 variant changes the Tyrosine at position 159 to a stop codon, denoted p.Tyr159Stop. This variant may result in an abnormal, truncated protein product or loss of protein from this allele through nonsense-mediated mRNA decay. However, c.475_476insG is not located in the A-band region of titin, where the majority of truncating mutations associated with DCM have been reported (Herman D et al., 2012). Other truncating TTN variants have been reported in approximately 3% of control alleles (Herman D et al., 2012). With the clinical and molecular information available at this time, we cannot definitively determine if c.475_476insG is a disease-causing mutation or a rare benign variant. The variant is found in CARDIOMYOPATHY panel(s).

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