ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.34537+3A>G

gnomAD frequency: 0.00002  dbSNP: rs1427570685
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000697804 SCV000826435 uncertain significance Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2018-04-10 criteria provided, single submitter clinical testing This sequence change falls in intron 149 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. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant is located in the I band of TTN (PMID: 25589632). Variants in this region of the TTN gene are typically not causative for cardiac disease, but may be relevant for neuromuscular disorders (PMID: 23975875). This variant has not been reported in the literature in individuals with TTN-related disease. 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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