Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000528228 | SCV000643700 | uncertain significance | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2017-03-14 | criteria provided, single submitter | clinical testing | This sequence change inserts 1 nucleotide in exon 33 of the TTN mRNA (c.7756dupA), causing a frameshift at codon 2586. This creates a premature translational stop signal in the TTN mRNA (p.Ile2586Asnfs*3). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 33402 amino acids of the TTN protein. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a TTN-related disease. In summary, although this is a novel truncating variant in the I-band, truncating variants in this region have been shown to be highly prevalent in the TTN gene in the general population and unaffected individuals (PMID: 26701604, 22335739, 25589632). However, truncating variants in the I-band have been reported in individuals affected with autosomal recessive centronuclear myopathy (PMID: 23975875). For these reasons it has been classified as a Variant of Uncertain Significance. |