Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000642730 | SCV000764417 | uncertain significance | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2017-10-05 | criteria provided, single submitter | clinical testing | In summary, although this is a novel truncating variant, truncating variants in this region of the TTN gene have been shown to be highly prevalent in the TTN gene in the general population and unaffected individuals (PMID: 26701604, 22335739). However, truncating mutations in this region have also been reported to cause autosomal recessive congenital myopathy (PMID: 23975875). Therefore without additional functional and/or genetic data, this variant has been classified as a Variant of Uncertain Significance. This variant has not been reported in the literature in individuals with TTN-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the I-band of the TTN gene (p.Glu3396Thrfs*26). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 32,596 amino acids of the TTN protein. |