Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
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 | |
Gene |
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. |