ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.53881+4C>T

gnomAD frequency: 0.00003  dbSNP: rs187632918
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000597103 SCV000709583 uncertain significance not provided 2017-06-29 criteria provided, single submitter clinical testing
Invitae RCV000810641 SCV000950863 uncertain significance Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2019-02-13 criteria provided, single submitter clinical testing This sequence change falls in intron 279 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 (rs187632918, ExAC 0.006%). This variant has not been reported in the literature in individuals with TTN-related disease. This variant is located in the A band of TTN (PMID: 25589632). Variants in this region may be relevant for cardiac or neuromuscular disorders (PMID: 25589632, 23975875). 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.
Athena Diagnostics Inc RCV000597103 SCV001146430 uncertain significance not provided 2018-08-29 criteria provided, single submitter clinical testing
GeneDx RCV000597103 SCV001795191 likely benign not provided 2019-12-17 criteria provided, single submitter clinical testing
Ambry Genetics RCV002456317 SCV002739513 uncertain significance Cardiovascular phenotype 2021-10-12 criteria provided, single submitter clinical testing The c.26686+4C>T intronic variant results from a C to T substitution 4 nucleotides after coding exon 106 in the TTN gene. This nucleotide position is poorly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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