Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001997643 | SCV002246161 | uncertain significance | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2021-06-14 | criteria provided, single submitter | clinical testing | 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. 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. This variant is located in the I band of TTN (PMID: 25589632). Variants in this region may be relevant for neuromuscular disorders, but have not been definitively shown to cause cardiomyopathy (PMID: 23975875). This variant has been observed in individual(s) with dilated cardiomyopathy (PMID: 31737537). This variant is not present in population databases (ExAC no frequency). This sequence change falls in intron 239 of the TTN gene. It does not directly change the encoded amino acid sequence of the TTN protein. It affects a nucleotide within the consensus splice site of the intron. |
| Ambry Genetics | RCV002398018 | SCV002712240 | uncertain significance | Cardiovascular phenotype | 2019-11-20 | criteria provided, single submitter | clinical testing | The c.17086+5G>A intronic variant results from a G to A substitution 5 nucleotides after coding exon 66 in the TTN gene. This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to weaken the efficiency of the native splice donor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Fulgent Genetics, |
RCV002492149 | SCV002776228 | uncertain significance | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J; Tibial muscular dystrophy; Myopathy, myofibrillar, 9, with early respiratory failure; Early-onset myopathy with fatal cardiomyopathy; Hypertrophic cardiomyopathy 9 | 2022-02-07 | criteria provided, single submitter | clinical testing |