Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000469038 | SCV000542750 | uncertain significance | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2017-04-26 | criteria provided, single submitter | clinical testing | This sequence change deletes 1 nucleotide from exon 54 of the TTN mRNA (c.15952delC), causing a frameshift at codon 5318. This creates a premature translational stop signal of the TTN mRNA (p.Leu5318Serfs*34). While this is not anticipated to result in nonsense mediated decay, it is expected to result in disrupted protein product. This variant is present in population databases (rs778392667, ExAC 0.002%) but has not been reported in the literature in individuals with a TTN-related disease. In summary, although this is a rare 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. |