Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000211871 | SCV000205734 | likely pathogenic | Primary dilated cardiomyopathy | 2018-06-19 | criteria provided, single submitter | clinical testing | The p.Trp976Arg variant in TTN has been reported in 1 family with DCM and segreg ated with disease in at least 8 affected relatives, including 2 obligate carrier s and at least one individual with early-onset cardiomyopathy who carried a trun cating variant (p.Arg19560X) in trans (Gerull 2002, reported as p.Trp930Arg; Her man 2012). This variant was absent from large population studies. In vitro funct ional studies suggest this variant may impact protein function (Hinson 2015). Co mputational prediction tools and conservation analysis suggest that the p.Trp976 Arg variant may impact the protein, though this information is not predictive en ough to determine pathogenicity. In summary, although additional studies are req uired to fully establish its clinical significance, the p.Trp976Arg variant is l ikely pathogenic. ACMG/AMP criteria applied: PP1_Strong, PM2, PP3, PS3_Supportin g. |
| OMIM | RCV000013486 | SCV000033733 | pathogenic | Dilated cardiomyopathy 1G | 2002-02-01 | no assertion criteria provided | literature only |