Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000464448 | SCV000542575 | uncertain significance | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2017-03-22 | criteria provided, single submitter | clinical testing | In summary, although this is a novel truncating variant, truncating variants have been shown to be highly prevalent in the TTN gene in the general population and unaffected individuals (PMID: 26701604, 22335739). Furthermore, this truncation is located outside of a clinically relevant region of the TTN gene (PMID: 25589632). For these reasons it has been classified as a Variant of Uncertain Significance. 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. This sequence change deletes 1 nucleotide from exon 173 of the TTN mRNA (c.36696delT), causing a frameshift at codon 12233. This creates a premature translational stop signal in the last exon of the TTN mRNA (p.Glu12233Lysfs*714). While this is not anticipated to result in nonsense mediated decay, it is expected to result in a truncated TTN protein. |