Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000040624 | SCV000064315 | uncertain significance | not specified | 2012-09-24 | criteria provided, single submitter | clinical testing | The Ile2314Thr variant in TTN has not been reported in the literature, but has b een identified by our laboratory in one individual with DCM and one individual w ith features of DCM (reduced ejection fraction and dilated left ventricle). Both probands carried several additional variants of unknown significance (LMM unpub lished data). Computational analyses (biochemical amino acid properties, conserv ation, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or agai nst an impact to the protein. In summary, additional information is needed to fu lly assess the clinical significance of the Ile2314Thr variant. |
| Ambry Genetics | RCV000619944 | SCV000735444 | uncertain significance | Cardiovascular phenotype | 2016-07-15 | criteria provided, single submitter | clinical testing | The p.I2268T variant (also known as c.6803T>C), located in coding exon 28 of the TTN gene, results from a T to C substitution at nucleotide position 6803. The isoleucine at codon 2268 is replaced by threonine, an amino acid with similar properties, and is located in the I-band region of the N2-B isoform of the titin protein. This variant was reported, as p.I2314T (c.6941T>C), in one individual with dilated cardiomyopathy (DCM) who also had variants in other cardiac-related genes (Pugh TJ et al. Genet. Med., 2014 Aug;16:601-8). This variant was previously reported in the SNPDatabase as rs397517708. Based on data from ExAC, the C allele has an overall frequency of approximately <0.01% (1/121336). This variant was not reported in population based cohorts in the following databases: NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |