Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
CHEO Genetics Diagnostic Laboratory, |
RCV000768942 | SCV000900315 | likely pathogenic | Cardiomyopathy | 2020-03-11 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001206660 | SCV001377980 | likely pathogenic | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2019-07-02 | criteria provided, single submitter | clinical testing | This sequence change results in a premature translational stop signal in the TTN gene (p.Thr23583Hisfs*15). While this is not anticipated to result in nonsense mediated decay, it is expected to create a truncated TTN protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with TTN-related conditions. ClinVar contains an entry for this variant (Variation ID: 626418). This variant is located in the A band of TTN (PMID: 25589632). Truncating variants in this region are significantly overrepresented in patients affected with dilated cardiomyopathy (PMID: 25589632). Truncating variants in this region have also been reported in individuals affected with autosomal recessive centronuclear myopathy (PMID: 23975875). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |