Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000036581 | SCV000060236 | likely pathogenic | Primary dilated cardiomyopathy | 2013-01-14 | criteria provided, single submitter | clinical testing | The Glu118Lys variant in TNNT2 has not been reported in the literature, but has been identified by our laboratory in 1 infant with congenital DCM and was not id entified in either parent, thus likely occurring de novo. This variant has also not been identified in large and broad European American and African American po pulations by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EV S), which increases the likelihood that the variant is pathogenic. However, we c annot exclude that it may be common in other populations. Glutamic acid (Glu) at position 118 is highly conserved in mammals and across evolutionarily distant s pecies, though dolphin has another amino acid at this position. The change to Ly sine (Lys) was predicted to be pathogenic using a computational tool clinically validated by our laboratory. This tool's pathogenic prediction is estimated to b e correct 94% of the time (Jordan 2011). In summary, the de novo occurrence and computational predictions support that this variant is likely pathogenic, though additional studies are needed to fully assess its clinical significance. |