ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.56963-3C>T (rs375979145)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV000208090 SCV000264292 uncertain significance Arrhythmogenic right ventricular cardiomyopathy 2015-10-23 criteria provided, single submitter clinical testing
GeneDx RCV000195040 SCV000718686 likely benign not specified 2017-04-24 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Genetic Services Laboratory, University of Chicago RCV000195040 SCV000249268 uncertain significance not specified 2015-01-20 criteria provided, single submitter clinical testing
Invitae RCV000642789 SCV000764476 uncertain significance Dilated cardiomyopathy 1G; Limb-girdle muscular dystrophy, type 2J 2018-05-04 criteria provided, single submitter clinical testing This sequence change falls in intron 291 of the TTN gene. It does not directly change the encoded amino acid sequence of the TTN protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs375979145, ExAC 0.002%). This variant has not been reported in the literature in individuals with TTN-related disease. ClinVar contains an entry for this variant (Variation ID: 212473). This variant identified in the TTN gene is located in the A band of the resulting protein (PMID: 25589632). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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