Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000220636 | SCV000272527 | likely pathogenic | Primary dilated cardiomyopathy | 2017-11-16 | criteria provided, single submitter | clinical testing | The c.324_325delinsGT (p.His109Tyr) variant in TNNT2 has not been reported in an y other individuals with cardiomyopathy, however another variant (c.325C>T) resu lting in the same amino acid change (p.His109Tyr) was identified by our laborato ry in one individual with early onset DCM, ventricular tachycardia and a family history of HCM and sudden death (Pugh 2014). Both variants are absent in large population databases. Parental testing for the c.324_325delinGT variant was nega tive indicating that the variant occurred de novo in this individual. In additio n, the histidine residue (His) at position 109 is highly conserved in mammals an d across evolutionary distant species and the change to amino acid Tyrosine (Tyr ) at this position is predicted to be pathogenic using a computational tool clin ically validated by our laboratory (Jordan 2011). In summary, although additiona l studies are required to fully establish its clinical significance, the p.His10 9Tyr variant is likely pathogenic. ACMG/AMP Criteria applied: PS2; PM2; PP3. |